Pyrazolotriazole derivatives

ABSTRACT

This invention relates to a pyrazolotriazole derivative represented by the general formula: ##STR1## wherein each symbol means as follows; R 1 , R 3  and R 4  : one of them represents hydrogen, tetrazolylated biphenylmethyl or lower alkyl, 
     R 2  : hydrogen, tetrazolylated biphenylmethyl, cycloalkyl or lower alkyl, and 
     R 5  and R 6  : these may be the same or different from each other, and each represents hydrogen, halogen, tetrazolylated biphenylmethyl, formyl, carboxyl, esterified carboxyl, cycloalkyl, lower alkoxy, lower alkoxycarbonyl, or lower alkyl which may be substituted with hydroxyl, formyl or carboxyl, 
     provided that at least one of R 1  to R 6  is tetrazolylated biphenylmethyl, and the broken lines mean that the pyrazolotriazole ring forms three double bonds, or a pharmaceutically acceptable salt thereof, and to a process for the production thereof, wherein the above compound (I) is useful for treating various diseases caused by the physiological function of angiotensin II.

TECHNICAL FIELD

This invention relates to novel pyrazolotriazole derivatives or saltsthereof which show an angiotensin II (to be referred to as AIIhereinafter) antagonism.

BACKGROUND ART

AII, a physiologically active peptide which shows a strong pressorreaction, has been regarded as a causal substance of hypertension invarious mammalian species.

There are a few known pathways for the formation of AII in the livingbody, including a typical pathway in which angiotensin I is formed fromangiotensinogen by the action of an enzyme, renin, and then convertedinto AII by the action of an angiotensin converting enzyme (ACE). Sincethe compound of the present invention inhibits expression of functionsAII by acting on the AII receptor, it is useful as an AII antagonist.

Examples of known AII antagonists include imidazole derivativesdisclosed in European Patent No. 253,310.

DISCLOSURE OF THE INVENTION

The inventors of the present invention have created various types ofcompounds and subjected them to screening and, as the result, foundpyrazolotriazole derivatives which have excellent anti-AII activity andwhose chemical structure is different from those of the prior artcompounds.

The pyrazolotriazole derivative of the present invention is representedby the following general formula. ##STR2## (Each symbol in the aboveformula means as follows; R¹, R³ and R⁴ : one of them represents ahydrogen atom, a biphenylmethyl group having a tetrazolyl group whichmay be substituted by aralkyl, or a lower alkyl group, and each of theremaining two has no substituent,

R² : a hydrogen atom, a biphenylmethyl group having a tetrazolyl groupwhich may be substituted by aralkyl, a cycloalkyl group, or a loweralkyl group which may be substituted by hydroxyl, lower alkoxy, carboxylor lower alkoxycarbonyl, and

R⁵ and R⁶ : these may be the same or different from each other, and eachrepresents a hydrogen atom, a halogen atom, a biphenylmethyl grouphaving a tetrazolyl group which may be substituted by aralkyl, a formylgroup, a carboxyl group, an esterified carboxyl group, a cycloalkylgroup, a lower alkoxy group, or a lower alkyl group which may besubstituted by hydroxyl, formyl, carboxyl, lower alkoxy or loweralkoxycarbonyl,

provided that at least one of R¹ to R⁶ is a biphenylmethyl group havinga tetrazolyl group which may be substituted by aralkyl and the brokenlines mean that the pyrazolotriazole ring forms three double bonds.)

The following describes the compound of the present invention in detail.

Unless otherwise indicated, the term "lower" as defined in the generalformula means a straight or branched carbon chain having 1 to 6 carbonatoms.

In consequence, illustrative examples of the "lower alkyl group" includemethyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl,tert-butyl, pentyl (amyl), iso-pentyl, neo-pentyl, tert-pentyl,1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, hexyl, iso-hexyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl,1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl,2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl,1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl,1-ethyl-2-methylpropyl and the like groups.

The lower alkyl group may be substituted with other substituent group.In the case of R², such a substituent group is hydroxyl, a lower alkoxy,carboxyl or a lower alkoxycarbonyl.

In the case of R⁵ and R⁶, the substituent group is hydroxyl, formyl,carboxyl, a lower alkoxy or a lower alkoxycarbonyl.

An optional position of a lower alkyl group can be substituted with oneor two of these substituent groups. Typical examples ofsubstituent-containing lower alkyl groups include methoxymethyl,ethoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 1-ethoxyethyl,2-ethoxyethyl, methoxycarbonylmethyl, 1-methoxycarbonylethyl,ethoxycarbonylmethyl, 1-ethoxycarbonylethyl, carboxymethyl,1-carboxyethyl, 2-carboxyethyl, 1-carboxypropyl, 2-carboxypropyl,3-carboxypropyl, dimethoxymethyl, diethoxymethyl, 2,2-dimethoxyethyl,2,2-diethoxyethyl, 3,3-dimethoxypropyl, 3,3-diethoxypropyl,3,3-dipropoxypropyl, 4,4-dimethoxybutyl, 4,4-diethoxybutyl,4,4-dipropoxybutyl, 5,5-dimethoxypentyl, 5,5-diethoxypentyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl,2-hydroxypropyl, 3-hydroxypropyl, formylmethyl, 1-formylethyl,2-formylethyl, 1-formylpropyl, 2-formylpropyl, 3-formylpropyl and thelike groups.

Examples of the "lower alkoxy group" include methoxy, ethoxy, propoxy,isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy(amyloxy), isopentyloxy, tert-pentyloxy, neopentyloxy, 2-methylbutoxy,1,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy and the like groups.

The "lower alkoxycarbonyl group" is a group in which a carbonyl group islinked to one of the aforementioned lower alkoxy groups, with itspreferred illustrative examples including methoxycarbonyl,ethoxycarbonyl, isopropoxycarbonyl and butoxycarbonyl.

Illustrative examples of the "cycloalkyl group" are those having 3 to 12carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl and thelike groups.

Examples of the "aralkyl group" include triphenylmethyl, benzyl,phenetyl, 1-phenylethyl and the like groups.

Illustrative examples of the "halogen atom" include iodine, bromine,chlorine, fluorine and the like atoms.

The esterified carboxyl group means a carboxylic acid residue esterifiedwith the aforementioned lower alkyl group, a group represented by aformula ##STR3## a group represented by a formula ##STR4## or a grouprepresented by a formula ##STR5##

In this instance, R⁷ in the above formula means a "lower alkylene orlower alkylidene group" of straight or branched carbon chain, and itsillustrative examples include methylene, ethylene, propylene,dimethylmethylene, tetramethylene, pentamethylene, hexamethylene,ethylidene, propylidene and the like groups.

Also, R⁸ means a "cycloalkyl group" or an "alkyl group". Examples of thecycloalkyl group include those described in the foregoing.

Examples of the alkyl group include long and medium chain hydrocarbonradicals having 7 to 12 carbon atoms, as well as the lower alkyl groupsdescribed in the foregoing. Preferred examples of the long and mediumchain alkyl groups include heptyl, 1,1-diethylpropyl, 1,1-dipropylbutyland the like groups.

Consequently, when X in the formula --R⁷ --OCO--X--R⁸ is a single bond,examples of this type of group include acetoxymethyl, 1-acetoxyethyl,2-acetoxyethyl, pivaloyloxymethyl, 2,2-dimethylpropanoyloxymethyl,1-(pivaloyloxy)ethyl, 1-(pivaloyloxy)propyl, 2-(pivaloyloxy)ethyl,2-(pivaloyloxy)propyl, (pivaloyloxy)propan-2-yl,2,2-diethylbutanoyloxymethyl, 2,2-dipropylpentanoyloxymethyl,cyclopropylcarbonyloxymethyl, cyclobutylcarbonyloxymethyl,cyclopentylcarbonyloxymethyl, cyclohexylcarbonyloxymethyl and the likegroups.

Also, when X in the formula is an oxygen atom, examples of such a typeof group include methoxycarbonyloxymethyl, 1-(methoxycarbonyloxy)ethyl,2-(methoxycarbonyloxy)ethyl, ethoxycarbonyloxymethyl,1-(ethoxycarbonyloxy)ethyl, 2-(ethoxycarbonyloxy)ethyl,propoxycarbonyloxymethyl, 1-(propoxycarbonyloxy)ethyl,2-(propoxycarbonyloxy)ethyl, cyclopropyloxycarbonyloxymethyl,1-(cyclopropyloxycarbonyloxy)ethyl, 2-(cyclopropyloxycarbonyloxy)ethyl,cyclobutyloxycarbonyloxymethyl, 1-(cyclobutyloxycarbonyloxy)ethyl,2-(cyclobutyloxycarbonyloxy)ethyl, cyclopentyloxycarbonyloxymethyl,1-(cyclopentyloxycarbonyloxy)ethyl, 2-(cyclopentyloxycarbonyloxy)ethyl,cyclohexyloxycarbonyloxymethyl, 1-(cyclohexyloxycarbonyl)ethyl,2-(cyclohexyloxycarbonyl)ethyl, cycloheptyloxycarbonyloxymethyl and thelike groups.

Typical examples of the group represented by the formula ##STR6## are asfollows.

Compound (I) of the present invention forms salts with acids and bases.Examples of its salts with acids include acid addition salts withmineral acids such as hydrochloric acid, hydrobromic acid, hydroiodicacid, sulfuric acid, nitric acid, phosphoric acid and the like or withorganic acids such as formic acid, acetic acid, propionic acid, oxalicacid, malonic acid, succinic acid, fumaric acid, maleic acid, lacticacid, malic acid, citric acid, tartaric acid, carbonic acid, picricacid, methanesulfonic acid, ethanesulfonic acid, glutamic acid and thelike.

Examples of base salts include those with inorganic bases such aslithium, sodium, potassium, magnesium, calcium, aluminium and the like,organic bases such as methylamine, ethylamine, ethanolamine and the likeand basic amino acids such as lysine, ornithine and the like, as well asammonium salts. In addition, the compound of the present invention maycontain asymmetric carbon atom(s) in some cases depending on the type ofsubstituent groups. In consequence, the compound of the presentinvention includes its various isomers such as geometrical isomers,tautomers, optical isomers and the like, either in the isolated form oras mixtures thereof.

(Production Process)

The compound of the present invention can be produced by employing thefollowing synthetic methods.

First method ##STR7## (In these formulae, R¹ to R⁶ are as described inthe foregoing, R¹⁰, R¹² and R¹³ : one of them represents a hydrogenatom, and each of the remaining two has no substituent,

R¹¹ : a hydrogen atom, a biphenylmethyl group having a tetrazolyl groupwhich may be substituted by aralkyl, a cycloalkyl group, or a loweralkyl group which may be substituted by hydroxyl, lower alkoxy, carboxylor lower alkoxycarbonyl, and

R¹⁴ and R¹⁵ : these may be the same or different from each other, andeach represents a hydrogen atom, a halogen atom, a biphenylmethyl grouphaving a tetrazolyl group which may be substituted by aralkyl, a formylgroup, a carboxyl group, an esterified carboxyl group, a cycloalkylgroup, a lower alkoxy group, a lower alkoxycarbonyl group, or a loweralkyl group which may be substituted by hydroxyl, formyl, carboxyl,lower alkoxy or lower alkoxycarbonyl,

provided that the broken lines mean that the pyrazolotriazole ring formsthree double bonds, and X represents a halogen atom or a sulfonic acidresidue and R⁹ represents an aralkyl group.)

By allowing a pyrazoloimidazole compound represented by the generalformula (III) to react with a lower alkyl halide (or sulfonate)represented by the general formula (IV) or with a biphenylmethyl halide(or sulfonate) represented by the general formula (V), the compound (I)of the present invention can be produced which has at least one moreadditional lower alkyl or biphenylmethyl group in comparison with thecompound (III).

This reaction is effected by stirring the compound (III) with thecompound (IV) and/or the compound (V) in corresponding amounts forreaction in an inert solvent at room temperature or with heating.

Preferably, a base may be added to the reaction system to accelerate thereaction.

Examples of the inert solvent include tetrahydrofuran, benzene,chloroform, toluene and the like. With regard to the base, potassiumbutoxide, potassium carbonate, sodium hydroxide, sodium hydride,metallic sodium, sodium methoxide, pyridine, triethylamine, picoline,lutidine, N,N-dimethylamine and the like may be used.

Second method (de-aralkylation) ##STR8## (Each symbol in the aboveformulae means as follows; R^(1b), R^(3b) and R^(4b) : one of themrepresents a hydrogen atom, a biphenylmethyl group having a tetrazolylgroup substituted by aralkyl, or a lower alkyl group, and each of theremaining two has no substituent,

R^(2b) : a hydrogen atom, a biphenylmethyl group having a tetrazolylgroup substituted by aralkyl, a cycloalkyl group, or a lower alkyl groupwhich may be substituted by hydroxyl, lower alkoxy, carboxyl or loweralkoxycarbonyl,

R^(5b) and R^(6b) : these may be the same or different from each other,and each represents a hydrogen atom, a halogen atom, a biphenylmethylgroup having a tetrazolyl group substituted by aralkyl, a formyl group,a carboxyl group, an esterified carboxyl group, a cycloalkyl group, alower alkoxy group, a lower alkoxycarbonyl group, or a lower alkyl groupwhich may be substituted by hydroxyl, formyl, carboxyl, lower alkoxy orlower alkoxycarbonyl,

provided that at least one of R^(1b) to R^(6b) is a biphenylmethyl grouphaving a tetrazolyl group substituted by aralkyl and the broken linesmean that the pyrazolotriazole ring forms three double bonds,

R^(1c), R^(3c) and R^(4c) : one of them represents a hydrogen atom, abiphenylmethyl group having a tetrazolyl group, or a lower alkyl group,and each of the remaining two has no substituent,

R^(2c) : a hydrogen atom, a biphenylmethyl group having a tetrazolylgroup, a cycloalkyl group, or a lower alkyl group which may besubstituted by hydroxyl, lower alkoxy, carboxyl or lower alkoxycarbonyl,and

R^(5c) and R^(6c) : these may be the same or different from each other,and each represents a hydrogen atom, a halogen atom, a biphenylmethylgroup having a tetrazolyl group, a formyl group, a carboxyl group, anesterified carboxyl group, a cycloalkyl group, a lower alkoxy group, alower alkoxycarbonyl group, or a lower alkyl group which may besubstituted by hydroxyl, formyl, carboxyl, lower alkoxy or loweralkoxycarbonyl,

provided that at least one of R^(1c) to R^(6c) is a biphenylmethyl grouphaving a tetrazolyl group and the broken lines mean that thepyrazolotriazole ring forms three double bonds.)

Among compounds of the present invention, the compound (VII) whosetetrazolyl group is not substituted by an aralkyl group can be obtainedby a catalytic reduction, a liquid ammonia reduction or an acidtreatment of the compound (VI) which has an aralkyl-substitutedtetrazolyl group. As to the acid, acetic acid, trifluoroacetic acid,trichloroacetic acid, hydrochloric acid, sulfuric acid, hydrobromicacid-acetic acid and the like may be used. This reaction is carried outgenerally in an organic solvent such as methanol, ethanol, acetone orthe like or in water, at room temperature or with heating (underreflux).

Third method

Among compounds of the present invention, a compound whose R² is a loweralkyl group which may be substituted by a carboxyl group can be obtainedby hydrolyzing its corresponding ester compound. Also, a compound inwhich each of R⁵ and R⁶ is a carboxyl group, a lower alkoxycarbonylgroup or a lower alkyl group which may be substituted with a carboxylgroup can be obtained by oxidizing its corresponding aldehyde compoundor hydrolyzing its corresponding ester compound.

(i) Oxidation

Oxidation of an aldehyde compound can be effected in the usual way, forexample, by allowing silver oxide to react with sodium hydroxide,potassium hydroxide, barium hydroxide or sodium carbonate in an inertsolvent cooled on an ice bath or at room temperature, adding thealdehyde compound to the resulting reaction solution and then effectingthe oxidation reaction at room temperature or under reflux. Examples ofthe inert solvent include distilled water, methanol, acetone and thelike.

Also, a corresponding carboxylic acid ester can be obtained by allowingan aldehyde compound of (I), whose R⁵ and R⁶ are the same or differentfrom each other and each representing a formyl group, to react withmanganese dioxide and sodium cyanide or potassium cyanide in an alcoholsuch as methanol, ethanol or the like at room temperature or withheating. In that case, it is desirable to add an acid to accelerate thereaction. Examples of useful acids include acetic acid, trifluoroaceticacid, hydrochloric acid, sulfuric acid, hydrobromic acid-acetic acid andthe like.

(ii) Hydrolysis

Hydrolysis of an ester compound can be effected in the usual way, forexample, by adding the ester compound to a basic inert solvent adjustedwith sodium hydroxide, potassium hydroxide or the like and subsequentlystirring or refluxing the mixture at room temperature or with heating.

Fourth method

When each of R⁵ and R⁶ of the compound of the present invention is alower alkyl group which may be substituted with hydroxyl group, thecompound can be obtained by reducing its corresponding aldehydecompound.

This reduction reaction can be effected in the usual way, for example,by dissolving an aldehyde compound in an inert solvent, adding areducing agent of metal hydride such as lithium aluminum hydride, sodiumborohydride, lithium borohydride, diisobutylaluminum hydride or the liketo the resulting solution and then stirring the mixture on an ice bathor at room temperature.

The thus produced compound of the present invention is then isolated andpurified in the free form or as a salt thereof.

Isolation and purification of the compound are carried out by employingusual chemical procedures such as extraction, concentration,distillation, crystallization, filtration, various chromatographictechniques and the like.

INDUSTRIAL APPLICABILITY

Since the compound of the present invention has an angiotensin II (AII)antagonism, it is useful for the treatment of various diseases caused bythe physiological activity of AII (hypertension, chronic heart failure,cardiac hypertrophy, arteriosclerosis (blood vessel wall hypertrophy),diabetic nephropathy, diabetic retinopathy, chronic glomerulonephritis,proliferative glomerulonephritis, glaucoma, amnesia, anxiety, benignprostatic hypertrophy and difficulty of urination accompanied thereby,peripheral circulatory failure, complicated or secondaryhyperaldosteronism, cerebrovascular disorder and the like). In addition,since the compound of the present invention also shows antagonismagainst AII which is formed without mediation by renin or ACE, morebroader hypotensive spectrum than those of ACE inhibitors and reninantagonists is expected.

The AII receptor-blocking activity of the compound of the presentinvention was measured based on its antagonistic effect (in vitro) onAII contraction of an excised rabbit aorta and its inhibitory effect (invivo) on AII-caused pressor reaction in a spinal cord-broken rat.

In vitro test:

A portion of rabbit aorta was excised to prepare a spiral strip specimenwhich was subsequently hung in Krebs-Hensseleit solution. This spiralstrip specimen causes a dose-dependent contraction when AII is added tothe Krebs-Hensseleit solution. Since a drug having AII receptor-blockingactivity causes shifting of the dose-response curve of the AII-basedcontraction to the high concentration side or reduces maximumcontraction by AII, a shifted width of the dose-response curve beforeand after the addition of each test drug or a maximum contractioninhibiting ratio was calculated.

The AII receptor-blocking activity was expressed by a pA₂ value(negative logarithmic value of the concentration of a blocking drugrequired to shift the dose-response curve to two times higherconcentration side) or a pD₂ ' value (negative logarithmic value of theconcentration of a blocking drug required to inhibit 50% of the maximumcontraction).

In vivo test:

An in vivo test was carried out by inserting cannulae into an aorta anda vein of a spinal cord-broken rat under artificial respiration. Thespinal cord-broken rat shows 50 to 70 mm Hg of continuous increase inthe blood pressure by continuous intravenous administration of AII (100ng/kg/min). Since a drug having AII receptor-blocking activity inhibitsthe AII-caused continuous blood pressure increase in a dose-dependentmanner, the AII antagonistic function of the test drug was examinedbased on the decreasing width of blood pressure after administration ofthe test drug. The AII receptor-blocking activity was expressed by anIC₃₀ value (a dose which decreases 30 mm Hg of blood pressure after theAII administration).

Results obtained by the above tests are shown in Tables 1 and 2.

                  TABLE 1                                                         ______________________________________                                        All receptor-blocking activity of the compounds of                            the present invention measured by the in vitro test                                           in vitro                                                      Examples          (pA.sub.2 value)                                                                        (pD.sub.2 ' value)                                ______________________________________                                        Dup 753           8.2                                                         (EP 253310, a compound                                                        disclosed in Example 89E)                                                     Example 52        8.65                                                        (the compound of the                                                          present invention)                                                            Example 53        8.50                                                        (the compound of the                                                          present invention)                                                            Example 57        8.52                                                        (the compound of the                                                          present invention)                                                            Example 95        8.85                                                        (the compound of the                                                          present invention)                                                            Example 96        9.16                                                        (the compound of the                                                          present invention)                                                            Example 98        9.02                                                        (the compound of the                                                          present invention)                                                            Example 99                  9.31                                              (the compound of the                                                          present invention)                                                            Example 100       8.81                                                        (the compound of the                                                          present invention)                                                            Example 101       9.25                                                        (the compound of the                                                          present invention)                                                            Example 102       9.14                                                        (the compound of the                                                          present invention)                                                            Example 105                 9.03                                              (the compound of the                                                          present invention)                                                            ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                        All receptor-blocking activity of the compounds of                            the present invention measured by the in vivo test                                             in vivo                                                      Examples         (IC.sub.30 mmHg (mg/kg, iv))                                 ______________________________________                                        Dup 753          0.1                                                          (EP 253310, a compound                                                        disclosed in Example 89E)                                                     Example 52       0.025                                                        (the compound of the                                                          present invention)                                                            Example 53       0.01                                                         (the compound of the                                                          present invention)                                                            Example 57       0.04                                                         (the compound of the                                                          present invention)                                                            Example 95       0.06                                                         (the compound of the                                                          present invention)                                                            Example 96       0.02                                                         (the compound of the                                                          present invention)                                                            Example 98       0.02                                                         (the compound of the                                                          present invention)                                                            ______________________________________                                    

Since the compound of the present invention has low toxicity, it issuitable for use as pharmaceutical drugs.

A pharmaceutical preparation containing, as an active ingredient, atleast one of the compound (I) or salts thereof according to the presentinvention is prepared making use of carriers, vehicles and otheradditives usually used for the preparation of drugs.

Carriers and vehicles for use in the production of the pharmaceuticalpreparation may be solids or liquids, which include for example lactose,magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic,olive oil, sesame oil, cacao butter, ethylene glycol and the like, aswell as other usually used substances.

The pharmaceutical preparation may be administered either by oraladministration in the form of tablets, pills, capsules, granules,powders, solutions or the like or by parenteral administration in theform of injections such as intravenous injection and intramuscularinjection or in the form of suppositories, percutaneous preparation, orthe like. Though the dose should be optionally decided in each casetaking into consideration symptoms, age, sex and the like of the patientto be treated, it may be in the range of from 10 to 1000 mg per day peradult in the case of oral administration, and the daily dose may be usedonce or by dividing it into 2 to 4.

Next, an example for the production of a pharmaceutical preparation foruse in the oral administration of the compound of the present inventionis described.

    ______________________________________                                        Preparation example (50 mg/tablet)                                            Composition                                                                   ______________________________________                                        Compound of Example 52 or 100                                                                            50 mg                                              Lactose                    72                                                 Corn Starch                18                                                 Hydroxypropyl Cellulose    5                                                  Carboxymethyl Cellulose Calcium                                                                          4.2                                                Magnesium Stearate         0.8                                                Total                     150 mg                                              ______________________________________                                    

Making use of a fluid-bed granulation coating machine (OhgawaraSeisaku-sho), 175 g of the compound of Example 52 or 100 was uniformlymixed with 252 g of lactose and 63 g of corn starch. To this was sprayed175 g of 10% hydroxypropyl cellulose solution to make the mixture intogranules. After drying, the granules were passed through a 20 meshsieve, mixed with 14.7 g of carboxymethyl cellulose calcium and 2.8 g ofmagnesium stearate and then made into tablets of 150 mg per tablet by arotary tabletting machine (Hata Tekko-sho) using a mortar stamp systemof 7.5 mm×8.4 R.

BEST MODE FOR CARRYING OUT THE INVENTION

The compound of the present invention and its production processdescribed in the foregoing are further illustrated in detail by thefollowing examples.

Since some of the starting compounds used in the Examples are novelcompounds, their production processes are shown as Reference Examples.

Reference Example 1 (Starting compound of Example 1) ##STR9## (A)N-(5-Propyl-1H-pyrazol-3-yl)acetamidine hydrochloride

A 11.5 g portion of 3-amino-5-propyl-1H-pyrazole was dissolved in 60 mlof acetonitrile, and 12.8 g of ethyl acetimidate hydrochloride was addedto the above solution with cooling on an ice bath. The resulting mixturewas stirred for 1 hour at the same temperature and then overnight atroom temperature.

After removing insoluble materials by filtration, the filtrate wasconcentrated under a reduced pressure, and the resulting residue wassubjected to silica gel column chromatography. Elution withmethanol-chloroform (1:9-1:4, v/v) gave 9.89 g of the title compound.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.61 (2H, m), 2.39 (3H, s), 2.60 (2H, t), 5.99 (1H, s)

(2) Mass spectrometric data (EI): 166 (M⁺) ##STR10##

(B) N-(5-Propyl-1H-pyrazol-3-yl)acetamidoxime

A 1.71 g portion of sodium was added to 60 ml of methanol to prepare asodium methoxide solution. A 4.96 g portion of hydroxylaminehydrochloride was added to the above solution and the thus formed sodiumchloride was removed by filtration to prepare a methanol solution ofhydroxylamine. On the other hand, 9.87 g ofN-(5-propyl-1H-pyrazol-3-yl)acetamidine hydrochloride was dissolved in50 ml of methanol and cooled on an ice bath.

To this was added dropwise the methanol solution of hydroxylamineprepared above, followed by overnight stirring at room temperature. Thereaction mixture was concentrated to a 1/3 to 1/4 volume under a reducedpressure, and the salts formed were removed by filtration and washedwith a small volume of methanol. Thereafter, the combined methanolsolution was concentrated under a reduced pressure and the thus obtainedresidue was subjected to silica gel column chromatography. Elution withmethanol-chloroform (1:9-1:4, v/v) gave 5.42 g of the title compound inthe form of colorless solid.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.57 (2H, m), 1.91 (3H, s), 2.48 (2H, t), 5.71 (1H, s)

(2) Mass spectrometric data (EI): 182 (M⁺) ##STR11##

(C) 2-Methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

A 5.38 g portion of N-(5-propyl-1H-pyrazol-3-yl)acetamidoxime wasdissolved in 45 ml of N,N-dimethylacetamide. With cooling on an icebath, to this were added 2.39 ml of pyridine and 5.63 g ofp-toluenesulfonic acid chloride, followed by 30 minutes of stirring atthe same temperature and additional 3 hours of stirring at roomtemperature. The resulting reaction mixture was added to 350 ml of waterand extracted with chloroform. After distilling off chloroform from theorganic layer under a reduced pressure, the thus obtained residue wasdissolved in 135 ml of methanol, mixed with 2.39 ml of pyridine and thenheated under reflux for 2 hours.

The reaction mixture was concentrated under a reduced pressure, and theresulting residue was subjected to silica gel column chromatography andelution was conducted with methanol-chloroform (1:19, v/v). Thereafter,fractions containing the compound of interest were concentrated under areduced pressure, and the thus formed colorless crystals were dispersedin diisopropyl ether and collected by filtration to give 2.51 g of thetitle compound. This compound was used in Example 1 and ReferenceExample 9.

(1) Melting point: 196°-197° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.91 (3H, t), 1.62 (2H, m), 2.37 (3H, s), 2.53 (2H, t), 5.53 (1H, s),12.24 (1H, brs)

(3) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 2 (Starting compound of Example 3) ##STR12## (A)N-(5-Methyl-1H-pyrazol-3-yl)propionamidine hydrochloride

A 13.8 g portion of 3-amino-5-methyl-1H-pyrazole was dissolved in 52 mlof acetonitrile, and 22.0 g of ethyl propionimidate hydrochloride wasadded to the above solution with cooling on an ice bath. The resultingmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature.

The solid material formed was collected by filtration and dissolved in amethanol-chloroform (1:4, v/v) mixed solvent. After removing insolublematerials by filtration, the resulting filtrate was concentrated under areduced pressure, and the thus obtained colorless solid material wasdispersed in an acetonitrile-diisopropyl ether (1:1, v/v) mixed solventand collected by filtration to give 15.1 g of the title compound.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.29 (3H, t), 2.27 (3H, s), 2.69 (2H, q), 6.03 (1H, s)

(2) Mass spectrometric data (EI): 152 (M⁺) ##STR13##

(B) N-(5-Methyl-1H-pyrazol-3-yl)propionamidoxime

In the same manner as the procedure of the step B of Reference Example1, 7.57 g of the title compound was obtained from 9.86 g ofN-(5-methyl-1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 2.15 (3H, s), 2.39 (2H, q), 5.69 (1H, s)

(2) Mass spectrometric data (EI): 168 (M⁺) ##STR14##

(C) 2-Ethyl-6-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 2.12 g of the title compound was obtained in the form of yellow solidfrom 7.55 g of N-(5-methyl-1H-pyrazol-3-yl)propionamidoxime. Thiscompound was used in Example 3 without further purification.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.26 (3H, t), 2.22 (3H, s), 2.73 (2H, q), 5.51 (1H, s), 12.24 (1H, brs)

(2) Mass spectrometric data (EI): 150 (M⁺)

Reference Example 3 (Starting compound of Example 4) ##STR15## (A)N-(5-Propyl-1H-pyrazol-3-yl)propionamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 4.20 g of the title compound was obtained from 4.32 g of3-amino-5-propyl-1H-pyrazole and 5.37 g of ethyl propionimidatehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.28 (3H, t), 1.62 (2H, m), 2.53-2.78 (4H, m), 6.02 (1H,s)

(2) Mass spectrometric data (EI): 180 (M⁺) ##STR16##

(B) N-(5-Propyl-1H-pyrazol-3-yl)propionamidoxime

In the same manner as the procedure of the step B of Reference Example1, 3.58 g of the title compound was obtained from 4.19 g ofN-(5-propyl-1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 0.94 (3H, t), 1.57 (2H, m), 5.70 (1H, s)

(2) Mass spectrometric data (EI): 196 (M⁺) ##STR17##

(C) 2-Ethyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 0.51 g of the title compound was obtained in the form of colorlesscrystals from 3.56 g of N-(5-propyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Melting point: 161°-163° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.91 (3H, t), 1.26 (3H, t), 1.61 (2H, m), 2.53 (2H, t), 2.72 (2H, q),5.52 (1H, s), 12.26 (1H, brs)

(3) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 4 (Starting compound of Example 5) ##STR18## (A)N-(5-Propyl-1H-pyrazol-3-yl)butylamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 4.30 g of the title compound was obtained from 4.02 g of3-amino-5-propyl-1H-pyrazole and 5.50 g of ethyl butylimidatehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.83-1.02 (6H, m), 1.45-1.96 (4H, m), 2.48-2.72 (4H, m), 6.02 (1H, s)

(2) Mass spectrometric data (EI): 194 (M⁺) ##STR19##

(B) N-(5-Propyl-1H-pyrazol-3-yl)butylamidoxime

In the same manner as the procedure of the step B of Reference Example1, 3.47 g of the title compound was obtained in the form of colorlesssolid from 4.21 g of N-(5-propyl-1H-pyrazol-3-yl)butylamidinehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.76-0.96 (6H, m), 1.24-1.77 (4H, m), 2.29-2.56 (4H, m), 5.71 (1H, s)

(2) Mass spectrometric data (EI): 210 (M⁺) ##STR20##

(C) 2,6-Dipropyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 0.88 g of the title compound was obtained in the form of colorlesscrystals from 3.42 g of N-(5-propyl-1H-pyrazol-3-yl)butylamidoxime.

(1) Melting point: 126°-128° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.91 (3H, t), 0.94 (3H, t), 1.41-1.83 (4H, m), 2.45-2.75 (4H, m), 5.52(1H, s), 12.24 (1H, brs)

(3) Mass spectrometric data (EI): 192 (M⁺)

Reference Example 5 (Starting compound of Example 6) ##STR21## (A)N-(5-Methyl-1H-pyrazol-3-yl)butylamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 24.4 g of the title compound was obtained from 15.9 g of3-amino-5-methyl-1H-pyrazole and 28.1 g of ethyl butylimidatehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.94 (3H, t), 1.74 (2H, m), 2.26 (3H, s) 2.62 (2H, t), 6.00 (mH, s)

(2) Mass spectrometric data (FAB): 167 (MH⁺) ##STR22##

(B) N-(5-Methyl-1H-pyrazol-3-yl)butylamidoxime

In the same manner as the procedure of the step B of Reference Example1, 21.7 g of the title compound was obtained from 24.3 g ofN-(5-methyl-1H-pyrazol-3-yl)butylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.83 (3H, t), 1.40 (2H, m), 2.16 (3H, s), 2.37 (2H, t), 5.69 (1H, s)

(2) Mass spectrometric data (FAB): 183 (MH⁺) ##STR23##

(C) 6-Methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 2.64 g of the title compound was obtained in the form of orange solidfrom 21.6 g of N-(5-methyl-1H-pyrazol-3-yl)butylamidoxime. This compoundwas used in Example 6 and Reference Example 10 without furtherpurification.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.71 (2H, m), 2.22 (3H, s), 2.67 (2H, t), 5.51 (1H, s),12.22 (1H, brs)

(2) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 6 (Starting compound of Example 7) ##STR24## (A)N-(1H-Pyrazol-3-yl)butylamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 13.8 g of the title compound was obtained from 10.3 g of3-amino-1H-pyrazole and 21.2 g of ethyl butylimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 1.76 (2H, m), 2.63 (2H, t), 6.23 (1H, s), 7.88 (1H, s)

(2) Mass spectrometric data (EI): 152 (M⁺) ##STR25##

(B) N-(1H-Pyrazol-3-yl)butylamidoxime

In the same manner as the procedure of the step B of Reference Example1, 3.33 g of the title compound was obtained in the form of colorlesssolid from 7.11 g of N-(1H-pyrazol-3-yl)butylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.82 (3H, t), 1.39 (2H, m), 5.93 (1H, s), 7.54 (1H, s)

(2) Mass spectrometric data (FAB): 169 (MH⁺) ##STR26##

(c) 2-Propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 0.92 g of the title compound was obtained in the form of colorlesscrystals from 3.33 g of N-(1H-pyrazol-3-yl)butylamidoxime. This compoundwas used as the starting compound of Example 7.

(1) Melting point: 145°-147° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.94 (3H, t), 1.74 (2H, m), 2.71 (2H, t), 5.74 (1H, d), 7.40 (1H, d),12.44 (1H, brs)

(3) Mass spectrometric data (EI): 150 (M⁺)

Reference Example 7 (Starting compound of Example 8) ##STR27## (A)N-(4-Methyl-1H-pyrazol-3-yl)butylamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 6.72 g of the title compound was obtained from 5.13 g of3-amino-4-methyl-1H-pyrazole and 9.07 g of ethyl butylimidatehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.97 (3H, t), 1.77 (2H, m), 2.09 (3H, d), 2.75 (2H, t), 7.67 (1H, q)

(2) Mass spectrometric data (EI): 166 (M⁺) ##STR28##

(B) N-(4-Methyl-1H-pyrazol-3-yl)butylamidoxime

In the same manner as the procedure of the step B of Reference Example1, 6.52 g of the title compound was obtained from 6.69 g ofN-(4-methyl-1H-pyrazol-3-yl)butylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.76 (3H, t), 1.30 (2H, m), 1.88 (3H, d), 2.17 (2H, t), 7.41 (1H, q)

(2) Mass spectrometric data (FAB): 183 (MH⁺) ##STR29##

(C) 7-Methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 1.54 g of the title compound was obtained in the form of colorlesscrystals from 6.50 g of N-(4-methyl-1H-pyrazol-3-yl)butylamidoxime. Thiscompound was used as the starting compound of Example 8.

(1) Melting point: 212°-214° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.94 (3H, t), 1.72 (2H, m), 2.08 (3H, d), 2.69 (2H, t), 7.18 (1H, q),12.30 (1H, brs)

(3) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 8 (Starting compound of Example 9) ##STR30## (A)3-Amino-4-methyl-5-propyl-1H-pyrazole

A two liter capacity three neck flask was cooled using a dry ice-acetonemixture and then charged with about 600 ml of liquid ammonia. Withmechanical vigorous agitation, 21.2 g of sodium amide was added at onceand, after 5 minutes thereof, 36.4 ml of propionitrile was addeddropwise spending 5 minutes, followed by 5 minutes of reaction.

To this was added dropwise 29.2 ml of methyl butanoate spending 5minutes, followed by 1 hour of reaction at the same temperature. In astream of argon, the reaction vessel was heated on a water bath of about40° C. to distill off ammonia. To the thus obtained white solid materialwere added 30 ml of ether and 150 ml of ice water, followed by theadjustment of the resulting mixture to strong acidity with 6Nhydrochloric acid aqueous solution.

The resulting organic layer was collected and mixed with 70 ml ofethanol and 22.0 ml of hydrazine monohydrate, ether was removed from themixture by distillation under normal pressure and then the thus obtainedethanol solution was heated overnight under reflux.

The reaction solution was concentrated under a reduced pressure, and theresulting residue was subjected to silica gel column chromatography.Elution with methanol-chloroform (1:19, v/v) gave 25.0 g of the titlecompound in the form of oily material.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.59 (2H, m), 1.85 (3H, s), 2.47 (2H, t)

(2) Mass spectrometric data (EI): 139 (M⁺) ##STR31##

(B) N-(4-Methyl-5-propyl-1H-pyrazol-3-yl)acetamidine hydrochloride

In the same manner as the procedure of the step A of Reference Example1, 19.0 g of the title compound was obtained from 24.6 g of3-amino-4-methyl-5-propyl-1H-pyrazole and 24.7 g of ethyl acetimidatehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.58 (2H, m), 2.01 (3H, s), 2.46 (3H, s), 2.55 (2H, t)

(2) Mass spectrometric data (FAB): 181 (MH⁺) ##STR32##

(C) N-(4-Methyl-5-propyl-1H-pyrazol-3-yl)acetamidoxime

In the same manner as the procedure of the step B of Reference Example1, 16.2 g of the title compound was obtained from 18.9 g ofN-(4-methyl-5-propyl-1H-pyrazol-3-yl)acetamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.55 (2H, m), 1.72 (3H, s), 1.80 (3H, s), 2.47 (2H, t)

(2) Mass spectrometric data (FAB): 197 (MH⁺) ##STR33##

(D) 2,7-Dimethyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of the step C of Reference Example1, 7.97 g of the title compound was obtained in the form of colorlesscrystals from 16.1 g ofN-(4-methyl-5-propyl-1H-pyrazol-3-yl)acetamidoxime. This was used as thestarting compound of Example 9.

(1) Melting point: 194°-195° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.58 (2H, m), 2.01 (3H, s), 2.35 (3H, s), 2.50 (2H, t),12.15 (1H, brs)

(3) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 9 (Starting compound of Example 10) ##STR34##7-Chloro-2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

A 677 mg portion of 2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas dissolved in a mixed solvent consisting of 40 ml of tetrahydrofuranand 80 ml of dichloromethane. A 550 mg portion of N-chlorosuccinimidewas added to the thus prepared solution and stirred at room temperaturefor 20 minutes, and the reaction mixture was washed twice with sodiumbicarbonate aqueous solution and then once with water.

The resulting organic layer was dried over anhydrous magnesium sulfateand the solvent was removed by distillation under a reduced pressure.Thereafter, the thus formed crystals were dispersed in diisopropyl etherand collected by filtration to give 671 mg of the title compound in theform of colorless crystals. This compound was used later in Example 10.

(1) Melting point: 198°-199° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.91 (3H, t), 1.63 (2H, m), 2.39 (3H, s), 2.55 (2H, t), 12.91 (1H, brs)

(3) Mass spectrometric data (EI): 198 (M⁺)

Reference Example 10 (Starting compound of Example 11) ##STR35##7-Chloro-6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole

In the same manner as the procedure of Reference Example 9, 556 mg ofthe title compound was obtained in the form of orange solid from 600 mgof 6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole. This compoundwas used in Example 11 without further purification.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.72 (2H, m), 2.20 (3H, s), 2.70 (2H, t), 12.87 (1H, brs)

(2) Mass spectrometric data (EI): 198 (M⁺)

Example 1 ##STR36##

A 1.75 g portion of 2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas dissolved in 70 ml of N,N-dimethylformamide, 1.19 g of potassiumt-butoxide was added to the solution, and the mixture was stirred for 30minutes at room temperature. The resulting reaction mixture was cooledon an ice bath and mixed with 6.52 g ofN-triphenylmethyl-5-[2-(4'-bromomethyl-biphenylyl)]tetrazole, and themixture was stirred for 1 hour at the same temperature and thenovernight at room temperature.

After removing the solvent by distillation under a reduced pressure, thethus obtained residue was mixed with ethyl acetate and washed twice withwater. The resulting ethyl acetate layer was dried over anhydrousmagnesium sulfate and concentrated under a reduced pressure, and thethus obtained residue was subjected to silica gel column chromatography.Elution with ethyl acetate-n-hexane (7:13-4:1, v/v) gave 0.38 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2-methyl-6-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 1a), 2.91 g of2-methyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 1b), 0.20 g of2-methyl-6-propyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 1c) and 1.89 g of a mixture (about 3:1) of2-methyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole (compound1d) and 2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 1a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.82 (3H, t), 1.38 (2H, m), 2.44 (2H, t), 2.48 (3H, s), 3.85 (2H, s),5.21 (2H, s)

(2) Mass spectrometric data (FAB): 1117 (MH⁺)

Compound 1b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.95 (3H, t), 1.67 (2H, m), 2.32 (3H, 2.63 (2H, t), 4.92 (2H, s), 5.27(1H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Compound 1c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.04 (3H, t) , 1.79 (2H, m), 1.86 (3H, s), 2.72 (2H, t), 3.82 (2H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Example 2 0 ##STR37##

The following compounds were obtained from 2.60 g of2,6-dimethyl-1H-pyrazolo[1,5-b][1,2,4]triazole in the same manner asdescribed in Example 1: 0.90 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2,6-dimethyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 2a), 3.90 g of2,6-dimethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 2b) (colorless crystals), 0.43 g of2,6-dimethyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole (compound 2c) and 2.92 g of2,6-dimethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 2d) (colorless crystals).

Compound 2a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.00 (3H, s), 2.48 (3H, s), 3.81 (2H, s), 5.18 (2H, s)

(2) Mass spectrometric data (FAB): 1089 (MH⁺)

Compound 2b;

(1) Melting point: 182°-183° C. (decomposition)

(2) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.31 (3H, s), 2.33 (3H, s), 4.91 (2H, s), 5.23 (1H, s)

(3) Mass spectrometric data (FAB): 613 (MH⁺)

Compound 2c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.87 (3H, s), 2.38 (3H, s), 3.79 (2H, s)

(2) Mass spectrometric data (FAB): 613 (MH⁺)

Compound 2d;

(1) Melting point: 192°-193° C. (decomposition)

(2) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.20 (3H, s), 2.46 (3H, s), 5.26 (2H, s), 5.89 (1H, s)

(3) Mass spectrometric data (FAB): 613 (MH⁺)

Example 3 ##STR38##

The following compounds were obtained from 524 mg of2-ethyl-6-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole in the same manner asdescribed in Example 1: 193 mg of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2-ethyl-6-methyl-5H-pyrazolo[1,5-b][1,2,4]triazole (compound 3a), 610 mgof2-ethyl-6-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 3b), 45 mg of2-ethyl-6-methyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 3c) and 649 mg of2-ethyl-6-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 3d).

Compound 3a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.39 (3H, t), 1.99 (3H, brs), 2.87 (2H, brs), 3.85 (2H, brs), 5.19 (2H,s)

(2) Mass spectrometric data (FAB): 1103 (MH⁺)

Compound 3b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.31 (3H, t), 2.31 (3H, s), 2.66 (2H, q), 4.92 (2H, s), 5.19 (1H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 3c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.95 (3H, t), 2.25 (2H, q), 2.37 (3H, s), 3.79 (2H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 3d;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.36 (3H, t), 2.19 (3H, s), 2.81 (2H, q), 5.27 (2H, s), 5.89 (1H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Example 4 ##STR39##

A 421 mg portion of 2-ethyl-6-n-propyl-1H-pyrazolo[1,5-b][1,2,4]triazoleused as the starting material was treated in the same manner asdescribed in Example 1, and the resulting residue was subjected tosilica gel column chromatography. Elution with ethyl acetate-n-hexane(7:13-1:1, v/v) gave 144 mg of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2-ethyl-6-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 4a), 504 mg of2-ethyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 4b) and 435 mg of2-ethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 4c).

Compound 4 a;

(1) Nuclear magnetic resonance spectrum (CDCl₃ TMS) δ (ppm):

0.80 (3H, t), 1.36 (3H, t), 2.39 (2H, t), 2.83 (2H, q), 3.85 (2H, s),5.20 (2H, s)

(2) Mass spectrometric data (FAB): 1131 (MH⁺)

Compound 4b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.95 (3H, t), 1.30 (3H, t), 1.67 (2H, m), 2.61-2.67 (4H, m), 4.92 (2H,s), 5.24 (1H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Compound 4c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.93 (3H, t), 1.36 (3H, t), 1.63 (2H, m), 2.48 (2H, t), 2.80 (2H, q),5.28 (2H, s), 5.90 (1H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 5 ##STR40##

The following compounds were obtained from 420 mg of2,6-dipropyl-1H-pyrazolo[1,5-b][1,2,4]triazole in the same manner asdescribed in Example 4: 112 mg of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2,6-dipropyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 5a), 456 mg of2,6-dipropyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 5b) and 370 mg of2,6-dipropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 5c).

Compound 5a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.80 (3H, t), 1.00 (3H, t), 1.35 (2H, m), 1.83 (2H, m), 2.40 (2H, t),2.80 (2H, t), 3.85 (2H, s), 5.20 (2H, s)

(2) Mass spectrometric data (FAB): 1145 (MH⁺)

Compound 5b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.93-1.00 (6H, m), 1.67 (2H, m), 1.76 (2H, m), 2.60-2.64 (4H, m), 4.93(2H, s), 5.22 (1H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Compound 5c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.94 (3H, t), 0.99 (3H, t), 1.82 (2H, m), 2.48 (2H, t), 2.74 (2H, t),5.28 (2H, s), 5.91 (1H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Example 6 ##STR41##

The following compounds were obtained from 316 mg of6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole in the same manneras described in Example 4: 157 mg of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-methyl-2-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 6a), 316 mg of6-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 6b) and 368 mg of a mixture (about 2:1) consisting of6-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl-]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 6c) and 6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 6a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.01 (3H, t), 1.84 (2H, m), 1.96 (3H, s), 2.78 (2H, t), 3.81 (2H, s),5.17 (2H, s)

Compound 6b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) 8 (ppm):

0.99 (3H, t), 1.77 (2H, m), 2.30 (3H, s), 2.63 (2H, t), 4.92 (2H, s),5.17 (1H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Example 7 ##STR42##

A 0.53 g portion of 2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole wastreated in the same manner as described in Example 1, and the resultingresidue was subjected to silica gel column chromatography. Elution withethyl acetate-n-hexane (2:3-1:1, v/v) gave 1.00 g of2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 7a) and 0.59 g of2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 7b).

Compound 7a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.01 (3H, t), 1.80 (2H, m), 2.66 (2H, t), 4.97 (2H, s), 5.37 (1H, d)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 7b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.02 (3H, t) , 1.85 (2H, m), 2.80 (2H, t), 5.20 (2H, s), 6.01 (1H, d)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Example 8 ##STR43##

A 307 mg portion of 7-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas treated in the same manner as described in Example 1, and theresulting residue was subjected to silica gel column chromatography.Elution with ethyl acetate-n-hexane (1:1-11:9, v/v) gave 148 mg of7-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 8a) and 790 mg of7-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 8b).

Compound 8a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.97 (3H, t), 1.75 (2H, m), 1.87 (3H, s), 2.60 (2H, t), 5.07 (2H, s),5.20 (1H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Compound 8b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.02 (3H, t), 1.87 (2H, m), 2.12 (3H, s), 2.83 (2H, t), 5.11 (2H, s) (2)Mass spectrometric data (FAB): 641 (MH⁺)

Example 9 ##STR44##

A 2.55 g portion of2,7-dimethyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was treated inthe same manner as described in Example 1, and the resulting residue wassubjected to silica gel column chromatography. Elution with ethylacetate-n-hexane (2:3-1:1, v/v) gave 1.15 g of2,7-dimethyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole (compound9a) and 2.65 g of2,7-dimethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 9b).

Compound 9a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.97 (3H, t), 1.68 (2H, m), 1.88 (3H, s), 2.25 (3H, s), 2.59 (2H, t),5.01 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Compound 9b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.90 (3H, t), 1.52 (2H, m), 2.14 (3H, s), 2.46 (3H, s), 2.48 (2H, t),5.22 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 10 ##STR45##

A 651 mg portion of7-chloro-2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was treatedin the same manner as described in Example 1, and the resulting residuewas subjected to silica gel column chromatography. Elution with ethylacetate-n-hexane (7:13, v/v) gave 603 mg of7-chloro-2-methyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 10a) and 225 mg of7-chloro-2-methyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 10b).

Compound 10a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.00 (3H, t), 1.76 (2H, m), 2.24 (3H, s), 2.69 (2H, t), 5.07 (2H, s)

(2) Mass spectrometric data (FAB): 674 (MH⁺)

Compound 10b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.94 (3H, t), 1.59 (2H, m), 2.50 (3H, s ), 2.61 (2H, t), 5.29 (2H, s)

(2) Mass spectrometric data (FAB): 675 (MH⁺)

Example 11 ##STR46##

A 500 mg portion of7-chloro-6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was treatedin the same manner as described in Example 10 to give 460 mg of7-chloro-6-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 11a) and 776 mg of7-chloro-6-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 11b).

Compound 11a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.94 (3H, t), 1.71 (2H, m), 2.34 (3H, s), 2.53 (2H, t), 5.08 (2H, s)

(2) Mass spectrometric data (FAB): 674 (M⁺)

Compound 11b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.99 (3H, t), 1.83 (2H, m), 2.19 (3H, s), 2.76 (2H, t), 5.26 (2H, s)

(2) Mass spectrometric data (FAB): 675 (MH⁺)

Example 12 ##STR47##

A mixture consisting of 1.00 g of2-methyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 1b), 54 ml of methanol and 6 ml of acetic acid was heatedunder reflux for 3 hours.

After removing the solvent by distillation under a reduced pressure, theresulting residue was mixed with toluene and again subjected todistillation under a reduced pressure. By adding ethyl acetate to theresulting residue for crystallization, 0.58 g of2-methyl-6-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals.

(1) Melting point: 233°-234° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.31        5.56    28.12                                         found:     66.14        5.68    28.03                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.59 (2H, m), 2.45 (3H, s), 2.51 (2H, t), 5.20 (2H, s),5.34 (1H, s), 7.12 (2H, d), 7.28 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 13 ##STR48##

A 1.00 g portion of2,6-dimethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 2b) was treated in the same manner as described in Example 12to give 0.56 g of2,6-dimethyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 239°-241° C. (decomposition)

(2) Elemental analysis data (for C₂₀ H₁₈ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.85        4.90    30.25                                         found:     64.79        4.95    29.97                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.20 (3H, s), 2.45 (3H, s), 5.19 (2H, s), 5.27 (1H, S), 7.12 (2H, d),7.27 (2H, d)

(4) Mass spectrometric data (FAB): 371 (MH⁺)

Example 14 ##STR49##

A 589 mg portion of2-ethyl-6-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 3b) was treated in the same manner as described in Example 12to give 317 mg of2-ethyl-6-methyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole in the form of colorless crystals.

(1) Melting point: 204°-206° C. (decomposition)

(2) Elemental analysis data (for C₂₁ H₂₀ N₈.0.2CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.12        5.41    27.87                                         found:     65.23        5.33    27.93                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.24 (3H, t), 2.20 (3H, s), 2.82 (2H, q), 5.20 (2H, s), 5.26 (1H, s),7.11 (2H, d), 7.25 (2H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 15 ##STR50##

A 484 mg portion of2-ethyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 4b) was treated in the same manner as described in Example 12,and the resulting residue was subjected to silica gel columnchromatography. Elution was conducted with a gradient from chloroformonly to methanol-chloroform (3:17, v/v) to give 290 mg of2-ethyl-6-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless amorphous foamy substance.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.24 (3H, t), 1.59 (2H, m), 2.82 (2H, q), 5.20 (2H, s),5.32 (1H, s), 7.11 (2H, d), 7.24 (2H, d)

(2) Mass spectrometric data (FAB): 413 (MH⁺)

Example 16 ##STR51##

A 423 mg portion of2,6-dipropyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 5b) was treated in the same manner as described in Example 15to give 154 mg of2,6-dipropyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless amorphous foamy substance.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 0.97 (3H, t), 1.59 (2H, m), 1.69 (2H, m), 2.78 (2H, t),5.21 (2H, s), 5.33 (1H, s), 7.11 (2H, d), 7.22 (2H, d)

(2) Mass spectrometric data (FAB): 427 (MH⁺)

Example 17 ##STR52##

A 310 mg portion of6-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 6b) was treated in the same manner as described in Example 12to give 136 mg of6-methyl-2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 156°-157° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.31        5.56    28.12                                         found:     66.36        5.74    27.74                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.96 (3H, t), 1.68 (2H, m), 2.20 (3H, s), 2.78 (2H, t), 5.21 (2H, s),5.26 (1H, s), 7.11 (2H, d), 7.24 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 18 ##STR53##

A 940 mg portion of2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 7b) was treated in the same manner as described in Example 12to give 473 mg of2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 103°-105° C.

(2) Elemental analysis data (for C₂₁ H₂₀ N₈.0.2CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.12        5.41    27.87                                         found:     65.27        5.41    28.06                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.97 (3H, t), 1.70 (2H, m), 2.81 (2H, t), 5.26 (2H, s), 5.51 (1H, d),7.11 (2H, d), 7.26 (2H, d), 7.38 (1H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 19 ##STR54##

A 143 mg portion of7-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 8a) was treated in the same manner as described in Example 12,and the resulting residue was crystallized from acetonitrile to give 63mg of7-methyl-2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 230°-231.5° C. (decomposition)

(2) Elemental analysis data (for C₂₂ H₂₂ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.31        5.56    28.12                                         found:     66.28        5.64    28.18                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.96 (3H, t), 1.68 (2H, m), 1.82 (3H, s) , 2.78 (2H, t), 5.33 (2H, s),7.10 (2H, d), 7.13 (2H, d), 7.18 (1H, s)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 20 ##STR55##

A 940 mg portion of2,7-dimethyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 9a) was treated in the same manner as described in Example 12to give 512 mg of2,7-dimethyl-6-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 231°-232° C. (decomposition)

(2) Elemental analysis data (for C₂₃ H₂₄ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.97        5.86    27.16                                         found:     66.91        5.90    27.06                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 1.64 (2H, m), 1.93 (3H, s), 2.43 (3H, s), 2.55 (2H, t),5.21 (2H, s), 7.12 (2H, d), 7.15 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 21 ##STR56##

A 560 mg portion of7-chloro-2-methyl-6-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 10a) was treated in the same manner as described in Example 15to give 300 mg of7-chloro-2-methyl-6-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless amorphous foamy substance.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.92 (3H, t), 1.63 (2H, m), 2.44 (3H, s), 2.54 (2H, t), 5.30 (2H, s),7.12 (2H, d), 7.21 (2H, d)

(2) Mass spectrometric data (FAB): 433 (MH⁺)

Example 22 ##STR57##

A 420 mg portion of7-chloro-6-methyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 11a) was treated in the same manner as described in Example 19to give 218 mg of7-chloro-6-methyl-2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 213°-214.5° C.

(2) Elemental analysis data (for C₂₂ H₂₁ ClN₈)

    ______________________________________                                                  C (%) H (%)      N (%)   Cl (%)                                     ______________________________________                                        calculated: 61.04   4.89       25.88 8.19                                     found:      60.92   5.03       25.97 8.24                                     ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.63 (2H, m), 2.20 (3H, s ), 2.75 (2H, t), 5.32 (2H, s),7.11 (2H, d), 7.19 (2H, d)

(4) Mass spectrometric data (FAB): 433 (MH⁺)

Example 23 ##STR58##

A 1.66 g portion of the mixed product obtained in Example 1 consisting(about 3:1) of2-methyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 1d) and 2-methyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas treated in the same manner as described in Example 12, the resultingresidue was subjected to silica gel column chromatography. Elution wasconducted with a gradient from chloroform only to methanol-chloroform(3:17, v/v) and then the eluted product was crystallized from ethylacetate to give 0.44 g of2-methyl-6-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 169.5°-171° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈.0.1CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.06        5.64    27.51                                         found:     66.08        5.53    27.74                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.61 (2H, m), 2.28 (3H, s), 2.69 (2H, t), 5.48 (2H, s),6.06 (1H, s), 7.06 (4H, s)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 24 ##STR59##

A 1.00 g portion of2,6-dimethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 2d) was treated in the same manner as described in Example 12to give 0.59 g of2,6-dimethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 225°-228° C.

(2) Elemental analysis data (for C₂₀ H₁₈ N₈.0.1CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.61        5.00    29.55                                         found:     64.39        5.02    29.41                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.27 (3H, s), 2.39 (3H, s), 5.47 (2H, s), 6.04 (1H, s), 7.07 (2H, d),7.10 (2H, d)

(4) Mass spectrometric data (FAB): 371 (MH⁺)

Example 25 ##STR60##

A 610 mg portion of2-ethyl-6-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 3d) was treated in the same manner as described in Example 12to give 316 mg of2-ethyl-6-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 206°-207.5° C. (decomposition)

(2) Elemental analysis data (for C₂₁ H₂₀ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.61        5.24    29.15                                         found:     65.41        5.18    28.85                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 2.38 (3H, s), 2.63 (2H, q), 5.47 (2H, s), 6.03 (1H, s),7.06 (2H, d), 7.10 (2H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 26 ##STR61##

A 417 mg portion of2-ethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 4c) was treated in the same manner as described in Example 12to give 180 mg of2-ethyl-6-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 172°-173.5° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.97        5.86    27.16                                         found:     66.80        5.87    27.12                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.93 (3H, t), 1.21 (3H, t), 1.61 (2H, m), 2.60-2.70 (4H, m), 5.48 (2H,s), 6.06 (1H, s), 7.06 (4H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 27 ##STR62##

A 347 mg portion of2,6-dipropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 5c) was treated in the same manner as described in Example 12to give 187 mg of2,6-dipropyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 172°-174° C.

(2) Elemental analysis data (for C₂₄ H₂₆ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              67.58        6.14    26.27                                         found:     67.52        6.30    26.21                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.88-0.95 (6H, m), 1.58-1.70 (4H, m), 2.58 (2H, t), 2.68 (2H, t), 5.48(2H, s), 6.06 (1H, s), 7.06 (4H, s)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 28 ##STR63##

A 359 mg portion of the mixed product obtained in Example 6 consisting(about 2:1) of6-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 6c) and 6-methyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas treated in the same manner as described in Example 23 to give 126 mgof6-methyl-2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 175°-177.5° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈.0.6H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.56        5.71    27.38                                         found:     64.48        5.61    27.38                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.67 (2H, m), 2.38 (3H, s), 2.58 (2H, t), 5.46 (2H, s),6.02 (1H, s), 7.06 (2H, d), 7.09 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 29 ##STR64##

A 568 mg portion of2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 7b) was treated in the same manner as described in Example 12to give 165 mg of2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 109°-111° C.

(2) Elemental analysis data (for C₂₁ H₂₀ N₈.0.2H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.00        5.30    28.88                                         found:     65.07        5.14    28.81                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.67 (2H, m), 2.59 (2H, t), 5.46 (2H, s), 6.20 (1H, d),7.07 (2H, d), 7.20 (2H, d), 7.92 (1H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 30 ##STR65##

A 783 mg portion of7-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 8b) was treated in the same manner as described in Example 19to give 412 mg of7-methyl-2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 193°-196° C. (decomposition)

(2) Elemental analysis data (for C₂₂ H₂₂ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.31        5.56    28.12                                         found:     66.13        5.57    28.04                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.67 (2H, m), 2.09 (3H, s), 2.58 (2H, t), 5.35 (2H, s),7.05 (2H, d), 7.18 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 31 ##STR66##

A 2.45 g portion of2,7-dimethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 9b) was treated in the same manner as described in Example 12to give 1.45 g of2,7-dimethyl-6-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 198°-200° C. (decomposition)

(2) Elemental analysis data (for C₂₂ H₂₄ N₈.0.1CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.71        5.93    26.60                                         found:     66.95        5.98    26.34                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.88 (3H, t), 1.47 (2H, m), 2.06 (3H, s), 2.27 (3H, s), 2.69 (2H, t),5.41 (2H, s), 7.02 (2H, d), 7.05 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 32 ##STR67##

A 198 mg portion of7-chloro-2-methyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 10b) was treated in the same manner as described in Example 12to give 81 mg of7-chloro-2-methyl-6-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 185°-187.5° C. (decomposition)

(2) Elemental analysis data (for C₂₂ H₂₁ ClN₈)

    ______________________________________                                                  C (%) H (%)     N (%)   Cl (%)                                      ______________________________________                                        calculated: 61.04   4.89      25.88 8.19                                      found:      61.09   4.92      25.88 8.34                                      ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.52 (2H, m), 2.30 (3H, s), 2.79 (2H, t), 5.54 (2H, s),7.07 (2H, d), 7.10 (2H, d)

(4) Mass spectrometric data (FAB): 433 (MH⁺)

Example 33 ##STR68##

A 740 mg portion of7-chloro-6-methyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 11b) was treated in the same manner as described in Example 12to give 414 mg of7-chloro-6-methyl-2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 120°-122° C.

(2) Elemental analysis data (for C₂₂ H₂₁ N₈.0.4CH₃ COOCH₂ CH₃)

    ______________________________________                                                  C (%) H (%)     N (%)   Cl (%)                                      ______________________________________                                        calculated: 60.55   5.21      23.94 7.57                                      found:      60.53   5.24      23.60 7.55                                      ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.68 (2H, m), 2.41 (3H, s), 2.61 (2H, t), 5.52 (2H, s),7.07 (2H, d), 7.15 (2H, d)

(4) Mass spectrometric data (FAB): 433 (MH⁺)

Example 34 ##STR69##

A 183 mg portion of2-methyl-6-propyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 1c) was treated in the same manner as described in Example 12,the resulting residue was dissolved in ethyl acetate with heating andthen the solution was cooled to collect the thus formed precipitate byfiltration, thereby giving 85 mg of2-methyl-6-propyl-7-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole in the form of colorless amorphoussolid.

(1) Elemental analysis data (for C₂₂ H₂₂ N₈.0.5CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.14        5.92    25.32                                         found:     65.07        5.80    25.56                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.53 (2H, m), 2.36 (3H, s), 3.78 (2H, s), 6.99 (2H, d),7.12 (2H, d), 12.20 (1H, s)

(3) Mass spectrometric data (FAB): 399 (MH⁺)

Example 35 ##STR70##

A 226 mg portion of2,6-dimethyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 2c) was treated in the same manner as described in Example 34to give 105 mg of2,6-dimethyl-7-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless amorphous solid.

(1) Elemental analysis data (for C₂₂ H₁₈ N₈.0.4CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.95        5.27    27.62                                         found:     63.63        5.16    27.77                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.15 (3H, s), 2.36 (3H, s), 3.77 (2H, s), 6.99 (2H, d), 7.12 (2H, d),12.22 (1H, s)

(3) Mass spectrometric data (FAB): 371 (MH⁺)

Example 36 ##STR71##

A 342 mg portion of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2-methyl-6-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 1a) was treated in the same manner as described in Example 12,the resulting residue was mixed with toluene and heated under reflux andthen the solution was cooled spontaneously to collect the thus formedprecipitate by filtration, thereby giving 182 mg of5,7-bis[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-2-methyl-6-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole in the form of colorlessamorphous solid.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.86 (3H, t), 1.40 (2H, m), 2.27 (3H, s), 2.74 (2H, t), 3.87 (2H, s),5.45 (2H, s)

(2) Mass spectrometric data (FAB): 632 (M⁺)

Example 37 ##STR72##

A 153 mg portion of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-methyl-2-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 6a) was treated in the same manner as described in Example 36to give 69 mg of5,7-bis[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-6-methyl-2-propyl-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of light yellow amorphous solid.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.66 (2H, m), 2.37 (3H, s), 2.57 (2H, t), 3.85 (2H, s),5.44 (2H, s)

(2) Mass spectrometric data (FAB): 633 (MH⁺)

Reference Example 11 (Starting compound for use in Example 38)

(A) With cooling at -78° C., ammonia gas was blown into a three neckflask to yield 600 ml of liquid ammonia. At -78° C., 19.0 g of sodiumamide was added to the flask and stirred for 10 minutes at the sametemperature, followed by gradual addition of 40 ml of n-butyronitrile ina dropwise manner and subsequent 10 minutes of stirring at -78° C. A 40ml portion of ethyl formate was gradually added in a dropwise manner tothe above reaction solution and the mixture was stirred for 1 hour at-78° C. With stirring, the reaction solution was warmed on a 40° C.water bath to distill off ammonia. The resulting residue was added to150 ml of ice water and adjusted to a pH value of less than 1 with 6Nhydrochloric acid. After extracting twice with 30 ml of ethyl ether, theresulting ether layers were combined and mixed with 100 ml of ethanol. A23 ml portion of hydrazine monohydrate was added to the resultingsolution at room temperature, and the mixture was heated at 80° C. todistill off ethyl ether and then subjected to over night reflux withheating. After distilling off the solvent under a reduced pressure, theresulting residue was subjected to silica gel column chromatography.Elution with 1:20 methanol-chloroform gave 12.8 g of3-amino-4-ethyl-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.16 (3H, t), 2.31 (2H, q), 7.10 (1H, s)

(2) Mass spectrometric data (EI): 111 (M⁺)

(B) A 7.9 g portion of triethyl orthopropionate was added to 5.0 g of3-amino-4-ethyl-1H-pyrazole and the mixture was heated at 120° C. todistill off the thus formed ethanol. After 3 hours of the reaction, thereaction solution was cooled down to room temperature and mixed with 30ml of methanol, 3.2 g of hydroxylamine hydrochloride and 4.6 g oftriethylamine in that order, followed by 3 hours of heating underreflux. After distilling off the solvent under a reduced pressure, theresulting residue was mixed with 150 ml of ethyl acetate and washedtwice with water, and the ethyl acetate layer was dried over anhydrousmagnesium sulfate and concentrated under a reduced pressure. Thereafter,the thus obtained residue was subjected to silica gel columnchromatography. Elution with methanol-chloroform (1:20, v/v) gave 3.9 gof N-(4-ethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.02 (3H, t), 1.18 (3H, t), 2.39 (2H, q), 2.41 (2H, q), 7.32 (1H, s)

(2) Mass spectrometric data (EI): 182 (M⁺)

(C) A 3.9 g portion of N-(4-ethyl-1H-pyrazol-3-yl)propionamidoxime wasdissolved in 20 ml of N,N-dimethylacetamide. With cooling on an icebath, to this were added 2.2 ml of pyridine and 4.1 g ofp-toluenesulfonic acid chloride, followed by 30 minutes of stirring atthe same temperature and additional 3 hours of stirring at roomtemperature. The resulting reaction mixture was added to 100 ml of waterand extracted with chloroform. After distilling off chloroform from theorganic layer under a reduced pressure, the thus obtained residue wasdissolved in 100 ml of methanol, mixed with 2.2 ml of pyridine and thenheated under reflux for 2 hours.

After distilling off the solvent under a reduced pressure, the resultingresidue was mixed with 100 ml of ethyl acetate and washed with water.Thereafter, the organic layer was dried over anhydrous magnesium sulfateand concentrated under a reduced pressure, and the resulting residue wassubjected to silica gel column chromatography. By carrying out elutionwith methanol-chloroform (1:20, v/v), 1.60 g of2,7-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained in the formof light yellow crystals.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19 (3H, t), 1.28 (3H, t), 2.50 (2H, q), 2.74 (2H, q), 7.21 (1H, s)

(2) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 12 (Starting compound for use in Example 39)

(A) In the same manner as described in the step (B) of Reference Example11, 730 mg of N-(4-ethyl-1H-pyrazol-3-yl)acetamidoxime was obtained from3.0 g of 3-amino-4-methyl-1H-pyrazole and 4.4 g of triethylorthoacetate.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.09 (3H, t), 1.71 (3H, s), 2.31 (2H, q), 7.41 (1H, s)

(2) Mass spectrometric data (EI): 168 (M⁺)

(B) In the same manner as the procedure of the step (C) of ReferenceExample 11, 580 mg of 7-ethyl-2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 2.8 g of N-(4-ethyl-1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19 (3H, t), 2.45 (3H, s), 2.50 (2H, q), 7.19 (1H, s)

(2) Mass spectrometric data (EI): 150 (M⁺)

Reference Example 13 (Starting compound for use in Example 40)

(A) In the same manner as described in the step (A) of Reference Example11, 17.2 g of 3-amino-4-n-propyl-1H-pyrazole was obtained from 40 ml ofn-valeronitrile.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.93 (3H, t), 1.37 (2H, m), 2.34 (2H, t), 7.09 (1H, s)

(2) Mass spectrometric data (EI): 125 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example11, 5.0 g of N-(4-n-propyl-1H-pyrazol-3-yl)propionamidoxime was obtainedfrom 9.0 g of 3-amino-4-n-propyl-1H-pyrazole and 13 g of triethylorthopropionate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.93 (3H, t), 1.00 (3H, t), 1.36-1.76 (2H, m), 2.21-2.50 (4H, m), 7.31(1H, s)

(2) Mass spectrometric data (EI): 182 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 1.9 g of2-ethyl-7-n-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from5.0 g of N-(4-n-propyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.28 (3H, t), 1.37-1.80 (2H, m) 2.46 (2H, t), 2.75 (2H,q), 7.20 (1H, s)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 14 (Starting compound for use in Example 41)

(A) In the same manner as described in the step (B) of Reference Example11, 4.5 g of N-(4-n-propyl-1H-pyrazol-3-yl)acetamidoxime was obtainedfrom 7.2 g of 3-amino-4-n-propyl-1H-pyrazole and 9.3 g of triethylorthoacetate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.88 (3H, t), 1.49 (2H, m), 1.71 (3H, s), 2.28 (2H, t), 7.40 (1H, s)

(2) Mass spectrometric data (EI): 182 (M⁺)

(B) In the same manner as the procedure of the step (C) of ReferenceExample 11, 1.5 g of2-methyl-7-n-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from4.5 g of N-(4-n-propyl-1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.59 (2H, m), 2.45 (2H, t), 2.93 (3H, s), 7.20 (2H, s)

(2) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 15 (Starting compound for use in Example 42)

(A) In the same manner as described in the step (A) of Reference Example11, 10.1 g of 3-amino-4-n-butyl-1H-pyrazole was obtained from 50 ml ofn-capronitrile.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.92 (3H, t), 1.17-1.67 (4H, m), 2.30 (2H, t), 7.10 (1H, s)

(2) Mass spectrometric data (EI): 139 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example11, 3.5 g of N-(4-n-butyl-1H-pyrazol-3-yl) propionamidoxime was obtainedfrom 6.2 g of 3-amino-4-n-butyl-1H-pyrazole and 7.8 g of triethylorthopropionate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.88 (6H, t), 1.24-1.56 (4H, m), 2.08-2.38 (4H, m), 7.39 (1H, s)

(2) Mass spectrometric data (EI): 210 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 500 mg of7-n-butyl-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from3.5 g of N-(4-n-butyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.28 (3H, t), 1.19-1.65 (4H, m), 2.47 (2H, t), 2.74 (2H,q), 7.19 (2H, s)

(2) Mass spectrometric data (EI): 192 (M⁺)

Reference Example 16 (Starting compound for use in Example 43)

(A) In the same manner as described in the step (A) of Reference Example11, 10.1 g of 3-amino-4-isopropyl-1H-pyrazole was obtained from 42 ml ofisobutyronitrile.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.18 (6H, d), 2.68 (1H, m), 7.10 (1H, s)

(2) Mass spectrometric data (EI): 125 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example11, 3.6 g of N-(4-isopropyl-1H-pyrazol-3-yl)propionamidoxime wasobtained from 5 g of 3-amino-4-isopropyl-1H-pyrazole and 7.0 g oftriethyl orthopropionate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.03 (3H, t), 1.20 (6H, d), 2.41 (2H, q), 2.81 (1H, m), 7.30 (1H, s)

(2) Mass spectrometric data (EI): 196 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 1.6 g of 2-ethyl-7-isopropyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from 3.6 g ofN-(4-isopropyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20-1.37 (9H, m), 2.37-3.02 (3H, m), 7.21 (1H, s)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 17 (Starting compound for use in Example 44)

(A) A 8.06 g portion of 3-amino-4-methyl-1H-pyrazole was dissolved in 30ml of acetonitrile and, with cooling on an ice bath, 12.9 g of ethylpropionimidate hydrochloride was added to the solution. The resultingmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature. After removing insoluble materials byfiltration, the resulting filtrate was concentrated under a reducedpressure, and the thus obtained residue was subjected to silica gelcolumn chromatography. Elution with methanol-chloroform (1:9-3:7, v/v)gave 8.40 g of N-(4-methyl-1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.30 (3H, t), 2.10 (3H, s), 2.81 (1H, q), 7.66 (1H, s)

(2) Mass spectrometric data (EI): 152 (M⁺)

(B) A 1.45 g portion of sodium was added to 50 ml of methanol to preparea sodium methoxide solution. A 4.22 g portion of hydroxylaminehydrochloride was added to the above solution and the thus formed sodiumchloride was removed by filtration to prepare a methanol solution ofhydroxylamine. On the other hand, 8.39 g ofN-(4-methyl-1H-pyrazol-3-yl)propionamidine hydrochloride was dissolvedin 50 ml of methanol and cooled on an ice bath.

To this was added dropwise the methanol solution of hydroxylamineprepared above, followed by overnight stirring at room temperature. Thereaction mixture was concentrated under a reduced pressure, and the thusobtained residue was subjected to silica gel column chromatography.Elution with methanol-chloroform (1:9, v/v) gave 6.73 g ofN-(4-methyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.89 (3H, s), 2.20 (2H, q), 7.39 (1H, s)

(2) Mass spectrometric data (EI): 168 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 3.38 g of 2-ethyl-7-methyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 6.61 g ofN-(4-methyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.27 (3H, t), 2.08 (3H, s), 2.74 (2H, q), 7.19 (1H, s), 12.31 (1H, brs)

(2) Mass spectrometric data (EI): 150 (M⁺)

Reference Example 18 (Starting compound for use in Example 45)

(A) A 10.7 g portion of 3-amino-4-methyl-1H-pyrazole was dissolved in 40ml of acetonitrile and, with cooling on an ice bath, 15.4 g of ethylacetimidate hydrochloride was added to the solution. The resultingmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature. The solid material thus formed wascollected by filtration and dissolved in a mixed solvent ofmethanol-chloroform (3:17, v/v).

After removing insoluble materials by filtration, the resulting filtratewas concentrated under a reduced pressure, and the thus obtained residuewas subjected to silica gel column chromatography. Elution withmethanolchloroform (1/4-3/7, v/v) gave 7.31 g ofN-(4-methyl-1-H-pyrazol-3-yl)acetamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.09 (3H, s), 2.48 (3H, s), 7.65 (1H, s)

(2) Mass spectrometric data (FAB): 139 (MH⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 5.45 g of N-(4-methyl-1H-pyrazol-3-yl)acetamidoxime was obtainedfrom 7.20 g of N-(4-methyl-1H-pyrazol-3-yl)acetamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.72 (3H, s), 1.89 (3H, s), 7.39 (1H, s)

(2) Mass spectrometric data (EI): 154 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 2.14 g of 2,7-dimethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasobtained from 5.38 g of N-(4-methyl-1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.07 (3H, s), 2.38 (3H, s), 7.19 (1H, s), 12.35 (1H, brs)

(2) Mass spectrometric data (EI): 136 (M⁺)

Reference Example 19 (Starting compound for use in Example 46)

(A) A 5.28 g portion of 3-amino-4-ethyl-1H-pyrazole was dissolved in 30ml of acetonitrile and, with cooling on an ice bath, 8.20 g of ethylisobutylimidate hydrochloride was added to the solution. The resultingmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature. The solid material thus formed wascollected by filtration and dissolved in a mixed solvent ofmethanol-chloroform (1/4, v/v). After removing insoluble materials byfiltration, the resulting filtrate was concentrated under a reducedpressure to give 7.29 g of N-(4-ethyl-1H-pyrazol-3-yl)isobutylamidinehydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.12 (3H, t), 1.33 (6H, d), 3.32 (1H, m), 7.71 (1H, s)

(2) Mass spectrometric data (EI): 180 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 6.10 g of N-(4-ethyl-1H-pyrazol-3-yl)isobutylamidoxime was obtainedfrom 7.21 g of N-(4-ethyl-1H-pyrazol-3-yl)isobutylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.97 (6H, d), 1.10 (3H, t), 2.31 (2H, q), 2.86 (1H, m), 7.41 (1H, s)

(2) Mass spectrometric data (EI): 196 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 2.52 g of7-ethyl-2-isopropyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from5.98 g of N-(4-ethyl-1H-pyrazol-3-yl)isobutylamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20 (3H, t), 1.32 (6H, d), 1.51 (2H, q), 3.07 (1H, m), 7.22 (1H, s),12.28 (1H, br)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 20 (Starting compound for use in Example 47)

(A) In the same manner as described in the step (A) of Reference Example18, 15.8 g of N-(5-ethyl-1H-pyrazol-3-yl)butylamidine hydrochloride wasobtained from 13.7 g of 3-amino-5-ethyl-1H-pyrazole and 21.1 g of ethylbutylimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 1.20 (3H, t), 1.77 (2H, m), 2.61-2.69 (4H, m), 6.05 (1H,s)

(2) Mass spectrometric data (EI): 180 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 12.0 g of N-(5-ethyl-1H-pyrazol-3-yl)butylamidoxime was obtainedfrom 15.7 g of N-(5-ethyl-1H-pyrazol-3-yl)butylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.83 (3H, t), 1.15 (3H, t), 1.40 (2H, m), 2.52 (2H, q), 5.70 (1H, s)

(2) Mass spectrometric data (EI): 196 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 3.87 g of 6-ethyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 12.0 g of N-(5-ethyl-1H-pyrazol-3-yl)butylamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.94 (3H, t), 1.19 (3H, t), 1.71 (2H, m), 2.59 (2H, q), 2.68 (2H, t),5.54 (1H, s), 12.28 (1H, brs)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 21 (Starting compound for use in Example 48)

(A) In the same manner as described in the step (A) of Reference Example17, 14.3 g of N-(5-ethyl-1H-pyrazol-3-yl)propionamidine hydrochloridewas obtained from 13.5 g of 3-amino-5-ethyl-1H-pyrazole and 18.9 g ofethyl propionimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20 (3H, t), 1.28 (3H, t), 2.55-2.81 (4H, m), 6.03 (1H, s)

(2) Mass spectrometric data (EI): 166 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 10.3 g of N-(5-ethyl-1H-pyrazol-3-yl)propionamidoxime was obtainedfrom 14.2 g of N-(5-ethyl-1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.96 (3H, t), 1.16 (3H, t), 2.31-2.65 (4H, m), 5.73 (1H, s)

(2) Mass spectrometric data (EI): 182 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 4.38 g of 2,6-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasobtained from 10.2 g of N-(5-ethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19 (3H, t), 1.27 (3H, t), 2.48-2.85 (4H, m), 5.55 (1H, s), 12.28 (1H,brs)

(2) Mass spectrometric data (EI): 164 (M⁺)

Reference Example 22 (Starting compound for use in Example 49)

(A) In the same manner as described in the step (A) of Reference Example19, 9.97 g of N-(5-ethyl-1H-pyrazol-3-yl)acetamidine hydrochloride wasobtained from 12.9 g of 3-amino-5-ethyl-1H-pyrazole and 16.3 g of ethylacetimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19 (3H, t), 2.41 (3H, s), 2.64 (2H, q), 6.00 (1H, s)

(2) Mass spectrometric data (EI): 152 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 8.28 g of N-(5-ethyl-1H-pyrazol-3-yl)acetamidoxime was obtained from13.3 g of N-(5-ethyl-1H-pyrazol-3-yl)acetamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.93 (3H, s), 2.52 (2H, q), 5.73 (1H, s)

(2) Mass spectrometric data (EI): 168 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 2.04 g of 6-ethyl-2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 8.18 g of N-(5-ethyl-1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19 (3H, t), 2.37 (3H, s), 2.58 (2H, q), 5.53 (1H, s), 12.27 (1H, brs)

(2) Mass spectrometric data (EI): 150 (M⁺)

Reference Example 23 (Starting compound for use in Example 50)

(A) In the same manner as described in the step (A) of Reference Example18, 14.5 g of N-(5-butyl-1H-pyrazol-3-yl)propionamidine hydrochloridewas obtained from 14.9 g of 3-amino-5-butyl-1H-pyrazole and 16.6 g ofethyl propionimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.06-1.74 (7H, m), 2.54-2.80 (4H, m), 6.02 (1H, s)

(2) Mass spectrometric data (EI): 194 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 11.0 g of N-(5-butyl-1H-pyrazol-3-yl)propionamidoxime was obtainedfrom 14.4 g of N-(5-butyl-1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 0.95 (3H, t), 5.72 (1H, s)

(2) Mass spectrometric data (EI): 210 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 3.08 g of 6-butyl-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 10.9 g of N-(5-butyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.27 (3H, t), 1.33 (2H, m), 1.59 (2H, m), 2.56 (2H, t),2.73 (2H, q), 5.53 (1H, s), 12.29 (1H, brs)

(2) Mass spectrometric data (EI): 192 (M⁺)

Reference Example 24 (Starting compound for use in Example 51)

(A) In the same manner as described in the step (A) of Reference Example17, 10.9 g of N-(1H-pyrazol-3-yl)propionamidine hydrochloride wasobtained from 10.2 g of 3-aminopyrazole and 19.0 g of ethylpropionimidate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.31 (3H, t), 2.73 (2H, q), 6.29 (1H, brs), 7.89 (1H, brs)

(2) Mass spectrometric data (EI): 138 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example17, 8.41 g of N-(1H-pyrazol-3-yl)propionamidoxime was obtained from 10.7g of N-(1H-pyrazol-3-yl)propionamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 2.41 (2H, q), 5.94 (1H, d), 7.53 (1H, d)

(2) Mass spectrometric data (EI): 154 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 11, 1.39 g of 2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasobtained from 8.30 g of N-(1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.28 (3H, t), 2.77 (2H, q), 5.74 (1H, d), 7.40 (1H, d), 12.43 (1H, brs)

(2) Mass spectrometric data (EI): 136 (M⁺)

Example 38 ##STR73##

A 1.67 g portion of 2,7-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasdissolved in 30 ml of N,N-dimethylformamide, and 1.3 g of potassiumt-butoxide was added to the solution. After stirring for 10 minutes atroom temperature, the reaction mixture was cooled on an ice bath andmixed with 6.8 g ofN-triphenylmethyl-5-[2-(4'-bromomethyl-biphenylyl)]tetrazole, and themixture was stirred for 30 minutes at the same temperature and thenovernight at room temperature. After removing the solvent bydistillation under a reduced pressure, the thus obtained residue wasmixed with ethyl acetate and washed with water.

The resulting ethyl acetate layer was dried over anhydrous magnesiumsulfate and concentrated under a reduced pressure, and the thus obtainedresidue was subjected to silica gel column chromatography. Elution withethyl acetate-n-hexane (1:1-7:3, v/v) gave 5.8 g of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole (compound 38a) and 310 mgof2,7-diethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 38b).

Compound 38a;

(1) Melting point: 157°-158.5° C. (decomposition)

(2) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.21 (3H, t), 1.40 (3H, t), 2.55 (2H, q), 2.87 (2H, q), 5.10 (2H, s)

(3) Mass spectrometric data (FAB): 641 (MH⁺)

Compound 38b;

(1) Melting point: 178°-179° C. (decomposition)

(2) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.04 (3H, t), 1.28 (3H, t), 2.31 (2H, q), 2.59 (2H, q), 5.06 (2H, s)

(3) Mass spectrometric data (FAB): 641 (MH⁺)

Example 39 ##STR74##

In the same manner as described in Example 38, 1.1 g of7-ethyl-2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 540 mg of7-ethyl-2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.22 (3H, t), 2.50 (3H, s), 2.53 (2H, q), 5.08 (2H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Example 40 ##STR75##

In the same manner as described in Example 38, 1.5 g of2-ethyl-7-n-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 500 mg of2-ethyl-7-n-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.92 (3H, t), 1.40 (3H, t), 1.61-1.68 (2H, m) 2.48 (2H, t), 2.88 (2H,q), 5.11 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 41 ##STR76##

In the same manner as described in Example 38, 1.7 g of2-methyl-7-n-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 500 mg of2-methyl-7-n-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.92 (3H, t), 1.67 (2H, m), 2.49 (2H, t), 2.55 (3H, s), 5.13 (2H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Example 42 ##STR77##

In the same manner as described in Example 38, 660 mg of7-n-butyl-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 490 mg of7-n-butyl-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.89 (3H, t), 1.34 (2H, m), 1.41 (3H, t), 1.61 (2H, m), 2.53 (2H, t),2.91 (2H, q), 5.13 (2H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Example 43 ##STR78##

In the same manner as described in Example 38, 1.2 g of2-ethyl-7-isopropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 500 mg of2-ethyl-7-isopropyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.26-1.29 (6H, m), 1.41 (3H, t), 2.91 (2H, q), 2.96 (1H, m), 5.13 (2H,s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 44 ##STR79##

In the same manner as described in Example 38, 1.5 g of2-ethyl-7-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 44a) and 330 mg of2-ethyl-7-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 44b) were obtained from 500 mg of2-ethyl-7-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 44a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.40 (3H, t), 2.11 (3H, s), 2.87 (2H, q), 5.09 (2H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 44b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.29 (3H, t), 1.91 (3H, s), 2.61 (2H, q), 5.05 (2H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Example 45 ##STR80##

In the same manner as described in Example 38, 1.5 g of2,7-dimethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 45a) and 560 mg of2,7-dimethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole (compound 45b) were obtained from 500mg of 2,7-dimethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 45a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.11 (3H, s), 2.52 (3H, s), 5.09 (2H, s)

(2) Mass spectrometric data (FAB): 613 (MH⁺)

Compound 45b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.94 (3H, s), 2.30 (3H, s), 5.07 (2H, s)

(2) Mass spectrometric data (FAB): 613 (MH⁺)

Example 46 ##STR81##

In the same manner as described in Example 38, 3.70 g of7-ethyl-2-isopropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 1.20 g of7-ethyl-2-isopropyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.20 (3H, t), 1.42 (6H, d), 2.57 (2H, q), 3.19 (1H, m), 5.10 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 47 ##STR82##

In the same manner as described in Example 38, 0.49 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-ethyl-2-propyl-5H-pyrazolo[1,5-b][1,2,4]triazole (compound 47a), 2.30 g of6-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 47b), 0.18 g of6-ethyl-2-propyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 47c) and 2.28 g of6-ethyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 47d) were obtained from 2.17 g of6-ethyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 47a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.92 (3H, t), 1.00 (3H, t), 1.84 (2H, m), 2.41 (2H, q), 2.79 (2H, t),3.85 (2H, s), 5.20 (2H, s)

(2) Mass spectrometric data (FAB): 1131 (MH⁺)

Compound 47b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.98 (3H, t), 1.23 (3H, t), 1.75 (2H, m), 2.61 (2H, t), 2.68 (2H, q),4.93 (2H, s), 5.23 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Compound 47c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.68 (3H, t), 1.33 (3H, t), 1.42 (2H, m), 2.22 (2H, t), 2.75 (2H, q),3.81 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Compound 47d;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.99 (3H, t), 1.21 (3H, t), 2.50 (2H, q), 2.75 (2H, t), 5.27 (2H, s),5.89 (1H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 48 ##STR83##

In the same manner as described in Example 38, 0.31 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-2,6-diethyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 48a), 2.60 g of2,6-diethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 48b), 0.20 g of2,6-diethyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 48c) and 2.04 g of2,6-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 48d) were obtained from 2.00 g of2,6-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 48a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.92 (3H, t), 1.37 (3H, t), 2.41 (2H, q), 2.84 (2H, q), 3.86 (2H, s),5.21 (2H, s)

(2) Mass spectrometric data (FAB): 1117 (MH⁺)

Compound 48b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.24 (3H, t), 1.29 (3H, t), 2.64 (2H, 2.69 (2H, q), 4.92 (2H, s), 5.25(1H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Compound 48c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.96 (3H, t), 1.32 (3H, t), 2.26 (2H, q), 2.74 (2H, q), 3.80 (2H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Compound 48d;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.22 (3H, t), 1.38 (3H, t), 2.53 (2H, 2.85 (2H, q), 5.30 (2H, s), 5.98(1H, s)

(2) Mass spectrometric data (FAB): 641 (MH⁺)

Example 49 ##STR84##

In the same manner as described in Example 38, 0.40 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-ethyl-2-methyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 49a), 2.96 g of6-ethyl-2-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 49b), 0.29 g of 6-ethyl-2-methyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 49c) and 1.75 g of6-ethyl-2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 49d) were obtained from 1.84 g of6-ethyl-2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 49a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.94 (3H, t), 2.43 (2H, q), 2.48 (3H, s), 3.84 (2H, s), 5.21 (2H, s)

(2) Mass spectrometric data (FAB): 1103 (MH⁺)

Compound 49b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.24 (3H, t), 2.34 (3H, s), 2.69 (2H, q), 4.94 (2H, s), 5.28 (1H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 49c;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.33 (3H, t), 1.89 (3H, s), 2.75 (2H, q), 3.81 (2H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Compound 49d;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.23 (3H, t), 2.48 (3H, s), 2.54 (2H, q), 5.29 (2H, s), 5.94 (1H, s)

(2) Mass spectrometric data (FAB): 627 (MH⁺)

Example 50 ##STR85##

In the same manner as described in Example 38, 0.61 g of5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-butyl-2-ethyl-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 50a), 2.52 g of6-butyl-2-ethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 50b), and 2.31 g of a mixture consisting (about 1:8) of6-butyl-2-ethyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 50c) and6-butyl-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 50d) were obtained from 2.34 g of6-butyl-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 50a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.79 (3H, t), 1.37 (3H, t), 2.42 (2H, t), 2.83 (2H, q), 3.85 (2H, s),5.21 (2H, s)

(2) Mass spectrometric data (FAB): 1145 (MH⁺)

Compound 50b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.91 (3H, t), 1.30 (3H, t), 1.38 (2H, m), 2.62-2.67 (4H, m), 4.92 (2H,s), 5.24 (1H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Example 51 ##STR86##

In the same manner as described in Example 38, 612 mg of2-ethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 51a) and 449 mg of2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 51b) were obtained from 378 mg of2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 51a;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.34 (3H, t), 2.69 (2H, q), 5.00 (2H, s), 5.40 (1H, s)

(2) Mass spectrometric data (FAB): 613 (MH⁺)

Compound 51b;

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.41 (3H, t), 2.90 (2H, q), 5.23 (2H, s), 6.07 (1H, d)

(2) Mass spectrometric data (FAB): 613 (MH⁺)

Example 52 ##STR87##

A mixture consisting of 5.8 g of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 38a), 180 ml of ethanol and 20 ml of acetic acid was heatedunder reflux for 3 hours. After removing the solvent by distillationunder a reduced pressure, the resulting residue was mixed with tolueneand again subjected to distillation removal of the solvent under areduced pressure. The thus obtained residue was mixed with ethyl acetateto give 3.3 g of crystals. By recrystallizing them from ethanol, 2.8 gof2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals.

(1) Melting point: 184°-186° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.31        5.56    28.12                                         found:     66.25        5.71    27.86                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21-1.27 (6H, m), 2.52 (2H, q), 2.65 (2H, q), 5.36 (2H, s), 7.07 (2H,d), 7.21 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 53 ##STR88##

In the same manner as described in Example 12, 500 mg of7-ethyl-2-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.1 g of7-ethyl-2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 215°-216° C.

(2) Elemental analysis data (for C₂₁ H₂₀ N.sub.₈.0.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.30        5.27    29.01                                         found:     65.49        5.29    28.85                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 2.28 (3H, s), 2.51 (2H, q), 5.36 (2H, s), 7.06 (2H, d),7.19 (2H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 54 ##STR89##

In the same manner as described in Example 12, 660 mg of2-ethyl-7-n-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.5 g of2-ethyl-7-n-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 134°-136° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈.0.3H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.10        5.93    26.81                                         found:     66.10        5.84    26.59                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.21 (3H, t), 1.60-1.66 (2H, m), 2.47 (2H, t), 2.63 (2H,q), 5.35 (2H, s), 7.06 (2H, d), 7.18 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 55 ##STR90##

In the same manner as described in Example 12, 270 mg of2-methyl-7-n-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.7 g of2-methyl-7-n-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 124°-126° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.45        5.81    26.90                                         found:     63.28        5.37    26.89                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.63 (2H, m), 2.28 (3H, s), 2.46 (2H, t), 5.35 (2H, s),7.06 (2H, d), 7.17 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 56 ##STR91##

In the same manner as described in Example 12, 170 mg of7-n-butyl-2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 440 mg of7-n-butyl-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 137°-139° C.

(2) Elemental analysis data (for C₂₄ H₂₆ N₈.0.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              67.30        6.17    26.16                                         found:     67.26        6.01    26.15                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.21 (3H, t), 1.31 (2H, m), 1.60 (2H, m), 2.49 (2H, t),2.64 (2H, q), 5.35 (2H, s), 7.06 (2H, d), 7.18 (2H, d)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 57 ##STR92##

In the same manner as described in Example 12, 640 mg of2-ethyl-7-isopropyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.2 g of2-ethyl-7-isopropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 143°-145° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈.0.2CH₃ CO₂ C₂ H₅)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.46        6.00    26.05                                         found:     66.65        5.97    25.87                                         ______________________________________                                         PG,132

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20-1.26 (9H, m), 2.64 (2H, q), 2.89 (2H, m), 5.35 (2H, s), 7.07 (2H,d), 7.20 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 58 ##STR93##

In the same manner as described in Example 12, 700 mg of2-ethyl-7-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.5 g of2-ethyl-7-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 44a).

(1) Melting point: 178°-180° C.

(2) Elemental analysis data (for C₂₁ H₂₀ N₈.0.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.55        5.25    29.01                                         found:     65.15        5.34    29.12                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.22 (3H, t), 2.09 (3H, s), 2.64 (2H, q), 5.35 (2H, s), 7.06 (2H, d),7.19 (2H, d)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 59 ##STR94##

In the same manner as described in Example 12, 650 mg of2,7-dimethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.3 g of2,7-dimethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 45a).

(1) Melting point: 261°-265° C.

(2) Elemental analysis data (for C₂₀ H₁₈ N₈.0.5H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.31        5.05    29.53                                         found:     63.67        5.13    29.14                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.08 (3H, s), 2.28 (3H, s), 5.35 (2H, s), 7.06 (2H, d), 7.17 (2H, d)

(4) Mass spectrometric data (FAB): 371 (MH⁺)

Example 60 ##STR95##

A mixture consisting of 2.38 g of7-ethyl-2-isopropyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole,90 ml of methanol and 10 ml of acetic acid was heated under reflux for 2hours. After removing the solvent by distillation under a reducedpressure, the thus obtained residue was subjected to silica gel columnchromatography. Elution with methanol-chloroform (1:9, v/v) gave 1.43 gof7-ethyl-2-isopropyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless amorphous foamy material.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 1.25 (6H, d), 2.96 (1H, m), 5.35 (2H, s), 7.07 (2H, d),7.21 (2H, d)

(2) Mass spectrometric data (FAB): 413 (MH⁺)

Example 61 ##STR96##

In the same manner as described in Example 12, 1.19 g of6-ethyl-2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 2.14 g of6-ethyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 47d).

(1) Melting point: 191°-193° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.97        5.86    27.16                                         found:     66.97        5.92    26.98                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.21 (3H, t), 1.67 (2H, m) ! 2.58 (2H, t), 2.72 (2H, q),5.48 (2H, s), 6.06 (1H, s), 7.05 (2H, d), 7.08 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 62 ##STR97##

In the same manner as described in Example 12, 1.03 g of2,6-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.95 g of2,6-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 48d).

(1) Melting point: 180°-182° C.

(2) Elemental analysis data (for C₂₂ H₂₂ N₈.0.2H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.92        5.62    27.87                                         found:     65.68        5.48    27.80                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 1.22 (3H, t), 2.64 (2H, q), 2.72 (2H, q), 5.49 (2H, s),6.06 (1H, s), 7.06 (2H, d), 7.09 (2H, d)

(4) Mass spectrometric data (FAB): 399 (MH⁺)

Example 63 ##STR98##

In the same manner as described in Example 12, 0.67 g of6-ethyl-2-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.66 g of6-ethyl-2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 49d).

(1) Melting point: 217°-219° C. (decomposition)

(2) Elemental analysis data (for C₂₁ H₂₀ N₈.0.4 H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.40        5.35    28.61                                         found:     64.56        5.28    28.16                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 2.28 (3H, s), 2.72 (2H, q), 5.47 (2H, s), 6.05 (1H, s),7.06 (4H, s)

(4) Mass spectrometric data (FAB): 385 (MH⁺)

Example 64 ##STR99##

In the same manner as described in Example 12, 1.04 g of6-butyl-2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 2.00 g of a mixtureconsisting (about 1:8) of6-butyl-2-ethyl-7-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 50c) and6-butyl-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 50d).

(1) Melting point: 183°-184.5° C.

(2) Elemental analysis data (for C₂₄ H₂₆ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              67.58        6.14    26.27                                         found:     67.52        6.10    26.15                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.88 (3H, t), 1.21 (3H, t), 1.35 (2H, m), 1.57 (2H, m), 2.63 (2H, q),2.70 (2H, t), 5.49 (2H, s), 6.06 (1H, s), 7.07 (4H, s)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 65 ##STR100##

In the same manner as described in Example 12, 83 mg of2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 200 mg of2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 51b).

(1) Melting point: 180°-183° C. (decomposition)

(2) Elemental analysis data (for C₂₀ H₁₈ N₈.0.1 CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.61        5.00    29.55                                         found:     64.19        5.03    29.33                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.31 (3H, t), 2.74 (2H, q), 5.46 (2H, s), 6.10 (1H, d), 7.10 (2H, d),7.26 (2H, d), 7.72 (1H, d)

(4) Mass spectrometric data (FAB): 371 (MH⁺)

Reference Example 25 (Starting compound for use in Example 66)##STR101##

(A) A 3.97 g portion of 3-amino-4-ethyl-1H-pyrazole was dissolved in 60ml of acetonitrile and, with cooling on an ice bath, 6.12 g of ethylbutylimidate hydrochloride was added to the solution. The thus preparedmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature.

The thus formed solid material was collected by filtration and dissolvedin a methanol-chloroform (1:4, v/v) mixed solvent. Thereafter, insolublematerials were removed by filtration, the resulting filtrate wasconcentrated under a reduced pressure and then the thus obtained residuewas subjected to silica gel column chromatography. Elution withmethanol-chloroform (1:9-1:4, v/v) gave 3.27 g ofN-(4-ethyl-1H-pyrazol-3-yl)butylamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.97 (3H, t), 1.12 (3H, t), 1.77 (2H, m), 2.44-2.86 (4H, m), 7.68 (1H,s)

(2) Mass spectrometric data (EI): 180 (M⁺)

(B) A 0.39 g portion of sodium was added to 15 ml of methanol to preparea sodium methoxide solution. A 1.18 g portion of hydroxylaminehydrochloride was added to the above solution and the thus formed sodiumchloride was removed by filtration to prepare a methanol solution ofhydroxylamine. On the other hand, 3.18 g ofN-(4-ethyl-1H-pyrazol-3-yl)butylamidine hydrochloride was dissolved in20 ml of methanol and cooled on an ice bath.

To this was added dropwise the methanol solution of hydroxylamineprepared above, followed by overnight stirring at room temperature. Thereaction mixture was concentrated under a reduced pressure, and the thusobtained residue was subjected to silica gel column chromatography.Elution with methanol-chloroform (1:9, v/v) gave 2.47 g ofN-(4-ethyl-1H-pyrazol-3-yl)butylamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.77 (3H, t), 1.09 (3H, t), 2.18 (2H, t), 2.30 (2H, q), 7.40 (1H, s)

(2) Mass spectrometric data (EI): 196 (M⁺)

(C) A 2.45 g portion of N-(4-ethyl-1H-pyrazol-3-yl)butylamidoxime wasdissolved in 20 ml of N,N-dimethylacetamide. With cooling on an icebath, to this were added 1.01 ml of pyridine and 2.38 g ofp-toluenesulfonic acid chloride, followed by 30 minutes of stirring atthe same temperature and additional 2 hours of stirring at roomtemperature.

The resulting reaction mixture was added to 100 ml of water andextracted with chloroform. After distilling off chloroform from theorganic layer under a reduced pressure, the thus obtained residue wasdissolved in 60 ml of methanol, mixed with 1.01 ml of pyridine and thenheated under reflux for 2 hours.

Thereafter, the reaction mixture was concentrated under a reducedpressure, and the resulting residue was subjected to silica gel columnchromatography. Elution with methanol-chloroform (3:97, v/v) gave 1.14 gof 7-ethyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.95 (3H, t), 1.20 (3H, t), 1.74 (2H, m), 2.50 (2H, q), 2.70 (2H, t),7.21 (1H, s), 12.33 (1H, brs)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 26 (Starting compound for use in Example 67)##STR102##

(A) A 4.92 g portion of 3-amino-4-ethyl-1H-pyrazole was dissolved in 25ml of acetonitrile and, with cooling on an ice bath, 8.30 g of ethylvalerimidate hydrochloride was added to the solution. The thus preparedmixture was stirred for 1 hour at the same temperature and thenovernight at room temperature.

Thereafter, the thus formed insoluble materials were removed byfiltration, the resulting filtrate was concentrated under a reducedpressure and then the thus obtained residue was subjected to silica gelcolumn chromatography. Elution with methanol-chloroform (1:9-1:4, v/v)gave 6.26 g of N-(4-ethyl-1H-pyrazol-3-yl)valeramidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.92 (3H, t), 1.12 (3H, t), 2.43-2.87 (4H, m), 7.69 (1H, s)

(2) Mass spectrometric data (EI): 194 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example25, 2.84 g of N-(4-ethyl-1H-pyrazol-3-yl)valeramidoxime was obtainedfrom 6.14 g of N-(4-ethyl-1H-pyrazol-3-yl)valeramidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.76 (3H, t), 2.12-2.43 (4H, m), 7.40 (1H, s)

(2) Mass spectrometric data (EI): 210 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 0.97 g of 2-butyl-7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 2.78 g of N-(4-ethyl-1H-pyrazol-3-yl)valeramidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.92 (3H, t), 1.20 (3H, t), 2.50 (2H, q), 2.72 (2H, t), 7.21 (1H, s),12.34 (1H, brs)

(2) Mass spectrometric data (EI): 192 (M⁺)

Reference Example 27 (Starting compound for use in Example 68)##STR103##

(A) A 15.1 g portion of 3-amino-4-ethyl-1H-pyrazole was dissolved in 80ml of acetonitrile and, with cooling on an ice bath, 23.2 g of ethylcyclopropanecarboxyimidate hydrochloride was added to the solution. Thethus prepared mixture was stirred for 1 hour at the same temperature andthen overnight at room temperature.

The thus formed solid material was collected by filtration and dissolvedin a methanol-chloroform (1:4, v/v) mixed solvent. Thereafter, insolublematerials were removed by filtration and the resulting filtrate wasconcentrated under a reduced pressure to give 13.6 g ofN-(4-ethyl-1H-pyrazol-3-yl)cyclopropanecarboxyamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.04-1.36 (7H, m), 2.42-2.67 (3H, m), 7.70 (1H, s)

(2) Mass spectrometric data (EI): 178 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example25, 12.1 g of N-(4-ethyl-1H-pyrazol-3-yl)cyclopropanecarboxyamidoximewas obtained from 15.2 g ofN-(4-ethyl-1H-pyrazol-3-yl)cyclopropanecarboxyamidine hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.43-0.65 (4H, m), 1.11 (3H, t), 1.47 (1H, brm), 2.33 (2H, q), 7.42 (1H,s)

(2) Mass spectrometric data (EI): 194 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 1.5 g of2-cyclopropyl-7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtainedfrom 17.9 g of N-(4-ethyl-1H-pyrazol-3-yl)cyclopropanecarboxyamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.92-1.27 (7H, m), 2.03 (1H, m), 2.48 (2H, q), 7.19 (1H, s), 12.30 (1H,brs)

(2) Mass spectrometric data (EI): 176 (M⁺)

Reference Example 28 (Starting compound for use in Example 69)##STR104##

(A) A one liter capacity three neck flask was cooled using a dryice-methanol mixture and then charged with about 300 ml of liquidammonia. With mechanical vigorous agitation, 13.2 g of sodium amide wasadded at once and, after 5 minutes thereof, 29.6 ml of butyronitrile wasadded dropwise spending 5 minutes, followed by 5 minutes of reaction. Tothis was added dropwise 16.6 ml of ethyl acetate spending 5 minutes,followed by 1 hour of reaction at the same temperature. In a stream ofargon, the reaction vessel was heated on a water bath of about 40° C. todistill off ammonia.

To the thus obtained white solid material were added 30 ml of ether and100 ml of ice water, followed by neutralization of the resulting mixturewith 6N hydrochloric acid aqueous solution. The resulting organic layerwas collected and mixed with 50 ml of ethanol and 16.9 ml of hydrazinemonohydrate. Ether was removed from the mixture by distillation undernormal pressure and then the thus obtained ethanol solution was heatedovernight under reflux.

The reaction solution was concentrated under a reduced pressure, and theresulting residue was subjected to silica gel column chromatography.Elution with methanol-chloroform (1:24, v/v) gave 12.2 g of3-amino-4-ethyl-5-methyl-1H-pyrazole in the form of oily material.

(1) Nuclear magnetic resonance spectrum (CDCl₃ -d₆, TMS) δ (ppm):

1.08 (3H, t), 2.13 (3H, s), 2.30 (2H, q), 5.53 (3H, brs)

(2) Mass spectrometric data (EI): 125 (M⁺)

(B) A 1.16 g portion of sodium was added to 50 ml of methanol to preparea sodium mathoxide solution. A 3.50 g portion of hydroxylaminehydrochloride was added to the above solution and the thus formed sodiumchloride was removed by filtration to prepare a methanol solution ofhydroxylamine.

On the other hand, a mixture consisting of 6.00 g of3-amino-4-ethyl-5-methyl-1H-pyrazole, 60 ml of toluene and 9.64 ml oftriethyl orthopropionate was heated overnight under reflux, and thesolvent was removed by distillation under a reduced pressure. Theresulting residue was dissolved in 60 ml of methanol. With cooling on anice bath, to this was added dropwise the methanol solution ofhydroxylamine prepared above, followed by overnight stirring at roomtemperature.

The reaction mixture was concentrated under a reduced pressure, and thethus obtained residue was subjected to silica gel column chromatography.Elution with methanol-chloroform (1:9, v/v) gave 3.78 g ofN-(4-ethyl-5-methyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.88 (3H, t), 1.00 (3H, t), 2.00-2.39 (7H, m)

(2) Mass spectrometric data (EI): 196 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 1.27 g of2,7-diethyl-6-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from3.74 g of N-(4-ethyl-5-methyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.16 (3H, t), 1.26 (3H, t), 2.15 (3H, s), 2.44 (2H, q), 2.71 (2H, q),12.12 (1H, brs)

(2) Mass spectrometric data (EI): 178 (M⁺)

Reference Example 29 (Starting compound for use in Example 70)##STR105##

(A) In the same manner as described in the step (A) of Reference Example28, 15.5 g of 3-amino-4-diethyl-1 H-pyrazole was obtained in the form ofcolorless solid from 26.6 ml of butyronitrile and 14.6 ml of methylpropionate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.09 (3H, t), 1.20 (3H, t), 2.32 (2H, q), 2.54 (2H, q), 5.29 (3H, brs)

(2) Mass spectrometric data (EI): 139 (M⁺)

(B) N-(4,5-Diethyl-1H-pyrazol-3-yl)propionamidine hydrochlorideintermediate obtained in the same manner as described in the step (A) ofReference Example 26 from 5.09 g of 3-amino-4,5-diethyl-1H-pyrazole wastreated in the same manner as the step (B) of Reference Example 25 togive 4.53 of N-(4,5-diethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.01 (3H, t), 1.15 (3H, t), 2.10-2.64 (6H, m)

(2) Mass spectrometric data (EI): 210 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 2.25 g of 2,6,7-triethyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 4.41 g ofN-(4,5-diethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.17 (3H, t), 1.18 (3H, t), 1.27 (3H, t), 2.33-2.85 (6H, m), 12.16 (1H,brs)

(2) Mass spectrometric data (EI): 192 (M⁺)

Reference Example 30 (Starting compound for use in Example 71)##STR106##

(A) In the same manner as described in the step (A) of Reference Example28, 17.7 g of 3-amino-4-ethyl-5-propyl-1H-pyrazole was obtained in theform of colorless solid from 32.5 ml of butyronitrile and 21.1 ml ofmethyl butanoate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.94 (3H, t), 1.09 (3H, t), 1.60 (2H, m), 2.32 (2H, q), 2.49 (2H, t),5.29 (3H, brs)

(2) Mass spectrometric data (EI): 153 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example28, 3.91 g of N-(4-ethyl-5-propyl-1H-pyrazol-3-yl)propionamidoxime wasobtained from 6.02 g of 3-amino-4-ethyl-5-propyl-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (6H, t), 1.00 (3H, t), 1.55 (2H, m) , 2.09-2.55 (6H, m)

(2) Mass spectrometric data (EI): 224 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 0.97 g of2,7-diethyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from3.89 g of N-(4-ethyl-5-propyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.16 (3H, t), 1.26 (3H, t), 1.57 (2H, m), 2.32-2.84 (6H,m), 12.11 (1H, brs)

(2) Mass spectrometric data (EI): 206 (M⁺)

Reference Example 31 (Starting compound for use in Example 72)##STR107##

(A) N-(1H-Pyrazol-3-yl)acetamidine hydrochloride intermediate obtainedin the same manner as described in the step (A) of Reference Example 25from 11.0 g of 3-amino-1H-pyrazole was treated in the same manner as thestep (B) of Reference Example 25 to give 5.50 g ofN-(1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.94 (3H, s), 5.96 (1H, d), 7.54 (1H, d)

(2) Mass spectrometric data (EI): 140 (M⁺)

(B) In the same manner as described in the step (C) of Reference Example25, 1.42 g of 2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtainedfrom 5.28 g of N-(1H-pyrazol-3-yl)acetamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.40 (3H, s), 5.72 (1H, d), 7.38 (1H, d), 12.41 (1H, brs)

(2) Mass spectrometric data (EI): 122 (M⁺)

Reference Example 32 (Starting compound for use in Example 73)##STR108##

A 1.50 g portion of 2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasdissolved in a mixed solvent consisting of 75 ml of tetrahydrofuran and150 ml of dichloromethane. This solution was mixed with 1.61 g ofN-chlorosuccinimide and stirred for 30 minutes at room temperature, andthe reaction mixture was washed twice with sodium bicarbonate aqueoussolution and then once with water.

The organic layer was dried over anhydrous magnesium sulfate and thesolvent was removed by distillation under a reduced pressure.Thereafter, the thus formed crystals were dispersed in diisopropyl etherand collected by filtration to give 1.34 g of7-chloro-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.29 (3H, t), 2.78 (2H, q), 7.49 (1H, s), 13.06 (1H, brs)

(2) Mass spectrometric data (EI): 170 (M⁺)

Reference Example 33 (Starting compound for use in Example 74)##STR109##

In the same manner as the procedure of Reference Example 32, 2.30 g of7-bromo-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from 2.52g of 2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole and 3.30 g ofN-bromosuccinimide.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.29 (3H, t), 2.79 (2H, q), 7.50 (1H, s), 13.03 (1H, brs),

(2) Mass spectrometric data (EI): 214 (M⁺)

Reference Example 34 (Starting compound for use in Example 75)##STR110##

(A) A mixture consisting of 58.9 g of methoxyacetonitrile and one literof ethyl formate was added, in a dropwise manner spending 1.5 hours, to111.5 g of potassium t-butoxide which was cooled on an ice bath andstirred vigorously. After 3 hours of stirring at the same temperature,600 ml of water was added to the reaction mixture. The resulting waterlayer was washed with 500 ml of ethyl acetate and then adjusted to pH5.8 with 2N hydrochloric acid aqueous solution.

To this were added 250 ml of ethanol and 60 ml of hydrazine monohydrate(80% in purity), followed by overnight heating under reflux. The solventwas removed by distillation under a reduced pressure, and the resultingresidue was mixed with 500 ml of a mixed solution of methanol andchloroform (1:9, v/v). Thereafter, insoluble materials were removed byfiltration, the resulting filtrate was concentrated under a reducedpressure, and then the thus obtained residue was subjected to silica gelcolumn chromatography. Elution with methanol-chloroform (3:47, v/v) gave6.61 g of 3-amino-4-methoxy-1H-pyrazole in the form of grey solid.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

3.61 (3H, s), 4.17 (2H, brs), 7.16 (1H, s), 10.88 (1H, brs)

(2) Mass spectrometric data (EI): 113 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example28, 8.61 g of N-(4-methoxy-1H-pyrazol-3-yl)propionamidoxime was obtainedfrom 7.92 g of 3-amino-4-methoxy-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.91 (3H, t), 2.22 (2H, q), 3.68 (3H, s), 7.44 (1H, s)

(2) Mass spectrometric data (FAB): 185 (MH⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 0.85 g of2-ethyl-7-methoxy-1H-pyrazolo[1,5-b][1,2,4]triazole was obtained from8.48 g of N-(4-methoxy-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.27 (3H, t), 2.73 (2H, q), 3.75 (3H, s), 7.22 (1H, s), 12.54 (1H, brs)

(2) Mass spectrometric data (EI): 166 (M⁺)

Reference Example 35 (Starting compound for use in Example 76)##STR111##

(A) In the same manner as described in the step (A) of Reference Example26, 6.53 g of ethylN-(4-ethyl-1H-pyrazol-3-yl)-3-amino-3-imino-propanoate hydrochloride wasobtained from 5.06 g of 3-amino-4-ethyl-1H-pyrazole and 9.80 g of ethyl3-ethoxy-3-imino-propanoate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.13 (3H, t), 1.23 (3H, t), 2.56 (2H, q), 4.12 (2H, s), 4.18 (2H, q),7.72 (1H, s)

(2) Mass spectrometric data (EI): 224 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example25, 3.31 g of ethylN-hydroxy-N'-(4-ethyl-1H-pyrazol-3-yl)-3-amino-3-imino-propanoate wasobtained from 6.44 g of ethylN-(4-ethyl-1H-pyrazol-3-yl)-3-amino-3-imino-propanoate hydrochloride.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.05 (3H, t), 1.09 (3H, t), 2.29 (2H, q), 3.31 (2H, s), 3.90 (2H, q),7.36 (1H, s)

(2) Mass spectrometric data (EI): 240 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 1.44 g of ethyl[7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole-2-yl]acetate was obtainedfrom 3.26 g of ethylN-hydroxy-N'-(4-ethyl-1H-pyrazol-3-yl)-3-amino-3-imino-propanoate.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20 (3H, t), 1.22 (3H, t), 2.51 (2H, q), 3.93 (2H, s), 4.16 (2H, q),7.27 (1H, s), 12.62 (1H, brs)

(2) Mass spectrometric data (EI): 222 (M⁺)

Reference Example 36 (Starting compound for use in Example 77)##STR112##

(A) In the same manner as described in the step (B) of Reference Example28, 9.11 g of N-(5-ethoxy-1H-pyrazol-3-yl)propionamidoxime was obtainedfrom 10.3 g of 3-amino-5-ethoxy-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.94 (3H, t), 1.27 (3H, t), 2.11-2.39 (2H, m) 4.05 (2H, q), 5.35 (1H, s)

(2) Mass spectrometric data (EI): 198 (M⁺)

(B) In the same manner as the procedure of the step (C) of ReferenceExample 25, 3.98 g of 6-ethoxy-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 9.04 g ofN-(5-ethoxy-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.26 (3H, t), 1.29 (3H, t), 2.72 (2H, q), 4.11 (2H, q), 5.20 (1H, s),12.30 (1H, brs)

(2) Mass spectrometric data (EI): 180 (M⁺)

Reference Example 37 (Starting compound for use in Example 78)##STR113##

(A) In the same manner as described in the step (A) of Reference Example28, 22.1 g of 3-amino-4-ethyl-5-methoxymethyl-1H-pyrazole was obtainedfrom 17.5 g of n-butyronitrile and 26.3 g of methyl methoxy acetate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.11 (3H, t), 2.36 (2H, t), 3.54 (3H, t), 4.41 (2H, s)

(2) Mass spectrometric data (EI): 155 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example28, 12.3 g of N-(4-ethyl-5 -methoxymethyl-1H-pyrazol-3-yl)propionamidoxime was obtained from 22 g of3-amino-4-ethyl-5-methoxymethyl-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.02 (3H, t), 2.20 (2H, q), 2.33 (2H, q), 3.23 (3H, s),3.33 (2H, s), 7.12 (1H, s), 9.40 (1H, s), 12.26 (1H, s)

(2) Mass spectrometric data (EI): 226 (M⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 1.2 g of2,7-diethyl-6-methoxymethyl-1H-pyrazolo[1,5-b][1,2,4]triazole wasobtained from 3.0 g ofN-(4-ethyl-5-methoxymethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.18 (3H, t), 1.28 (3H, t), 2.51 (2H, q), 2.74 (2H, q), 3.21 (3H, s),4.34 (2H, s), 12.33 (1H, s)

(2) Mass spectrometric data (EI): 208 (M⁺)

Reference Example 38 (Starting compound for use in Example 79)##STR114##

(A) In the same manner as described in the step (A) of Reference Example28, 23.5 g of 3-amino-4-ethyl-5-diethoxymethyl-1H-pyrazole was obtainedfrom 17 ml of n-butyronitrile and 25 ml of ethyl diethoxy acetate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.10 (3H, t), 1.21 (6H, t), 2.40 (2H, q), 3.57 (4H, q), 5.61 (1H, s)

(2) Mass spectrometric data (EI): 213 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example28, 10.0 g ofN-(4-ethyl-5-diethoxymethyl-1H-pyrazol-3-yl)propionamidoxime wasobtained from 10.0 g of 3-amino-4-ethyl-5-diethoxymethyl-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.04 (3H, t), 1.12 (3H, t), 1.24 (6H, t), 2.41-2.48 (4H, m), 3.56-3.61(4H, m), 5.67 (1H, s)

(2) Mass spectrometric data (FAB): 285 (MH⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 1.3 g of2,7-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde wasobtained from 3.0 g ofN-(4-ethyl-5-diethoxymethyl-1H-pyrazol-3-yl)propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 1.31 (3H, t), 2.82 (4H, q), 9.88 (1H, s), 12.89 (1H, brs)

(2) Mass spectrometric data (FAB): 193 (MH⁺)

Reference Example 39 (Starting compound for use in Example 80)##STR115##

(A) In the same manner as described in the step (A) of Reference Example28, 3.9 g of 3-amino-4-ethyl-5-(2,2-dimethoxyethyl)-1H-pyrazole wasobtained from 23.4 g of n-butyronitrile and 25 g of methyl 3,3-dimethoxypropionate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.09 (3H, t), 2.32 (2H, q), 2.82 (2H, d), 3.38 (6H, s), 4.50 (1H, t)

(2) Mass spectrometric data (EI): 199 (M⁺)

(B) In the same manner as described in the step (B) of Reference Example28, 1.4 g ofN-(4-ethyl-5-(2,2-dimethoxyethyl)-1H-pyrazol-3-yl)propionamidoxime wasobtained from 3.8 g of3-amino-4-ethyl-5-(2,2-dimethoxyethyl)-1H-pyrazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.87 (3H, t), 1.01 (3H, t), 2.21-2.23 (2H, br), 2.31 (2H, q), 2.77 (2H,d), 3.24 (6H, s), 4.51 (1H, t), 7.05 (1H, s), 9.39 (1H, s), 11.89 (1H,s)

(2) Mass spectrometric data (FAB): 271 (MH⁺)

(C) In the same manner as the procedure of the step (C) of ReferenceExample 25, 500 mg of2,7-diethyl-6-(2,2-dimethoxyethyl)-1H-pyrazolo[1,5-b][1,2,4]triazole wasobtained from 1.4 g ofN-(4-ethyl-5-(2,2-dimethoxyethyl-1H-pyrazol-3-yl]propionamidoxime.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.16 (3H, t), 1.27 (3H, t), 2.45 (2H, q) , 2.72 (2H, q), 2.78 (2H, d),3.22 (6H, s), 4.58 (1H, t), 12.19 (1H, s)

(2) Mass spectrometric data (FAB): 253 (MH⁺)

Example 66 ##STR116##

A 0.60 g portion of 7-ethyl-2-propyl-1H-pyrazolo[1,5-b][1,2,4]triazolewas dissolved in 25 ml of N,N-dimethylformamide, and the resultingsolution was mixed with 0.40 g of potassium t-butoxide and stirred for15 minutes at room temperature. With cooling on an ice bath, to thereaction mixture was added 2.07 g ofN-triphenylmethyl-5-[2-(4'-bromomethyl-biphenylyl)]tetrazole, followedby 1 hour of stirring at the same temperature and subsequent overnightstirring at room temperature.

After removing the solvent by distillation under a reduced pressure, thethus obtained residue was mixed with ethyl acetate and washed withwater. The resulting ethyl acetate layer was dried over anhydrousmagnesium sulfate and concentrated under a reduced pressure, and thethus obtained residue was subjected to silica gel column chromatography.Elution with ethyl acetate-n-hexane (9:11, v/v) gave 1.41 g of7-ethyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.02 (3H, t), 1.21 (3H, t), 1.86 (2H, m), 2.55 (2H, q), 2.81 (2H, t),5.11 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 67 ##STR117##

In the same manner as described in Example 66, 0.96 g of2-butyl-7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 0.61 g of2-butyl-7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.96 (3H, t), 1.21 (3H, t), 1.45 (2H, m), 1.82 (2H, m), 2.56 (2H, q),2.84 (2H, t), 5.11 (2H, s)

(2) Mass spectrometric data (FAB): 699 (MH⁺)

Example 68 ##STR118##

In the same manner as described in Example 66, 1.70 g of2-cyclopropyl-7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole was obtained from 1.04 g of2-cyclopropyl-7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.96-1.10 (4H, m), 1.19 (3H, t), 2.13 (1H, m), 2.53 (2H, q), 5.07 (2H,s)

(2) Mass spectrometric data (FAB): 653 (MH⁺)

Example 69 ##STR119##

In the same manner as described in Example 66, 1.76 g of2,7-diethyl-6-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 0.70 g of2,7-diethyl-6-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.27 (3H, t), 1.38 (3H, t), 2.12 (3H, s), 2.57 (2H, q), 2.86 (2H, q),5.24 (2H, s)

(2) Mass spectrometric data (FAB): 655 (MH⁺)

Example 70 ##STR120##

In the same manner as described in Example 66, 2.50 g of2,6,7-triethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 1.25 g of2,6,7-triethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.10 (3H, t), 1.29 (3H, t), 1.37 (3H, t), 2.50 (2H, q), 2.58 (2H, q),2.84 (2H, q), 5.24 (2H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Example 71 ##STR121##

In the same manner as described in Example 66, 1.08 g of2,7-diethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole was obtained from 0.66 g of2,7-diethyl-6-propyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.91 (3H, t), 1.31 (3H, t), 1.37 (3H, t), 1.51 (2H, m), 2.49 (2H, t),2.58 (2H, q), 2.85 (2H, q), 5.24 (2H, s)

(2) Mass spectrometric data (FAB): 683 (MH⁺)

Example 72 ##STR122##

In the same manner as described in Example 66, 2.61 g of2-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 72a) and 1.15 g of2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 72b) were obtained from 1.11 g of2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 72a:

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.37 (3H, s), 4.97 (2H, s), 5.43 (1H, d)

(2) Mass spectrometric data (FAB): 599 (MH⁺)

Compound 72b

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

2.51 (3H, s), 5.20 (2H, s), 6.01 (1H, d)

(2) Mass spectrometric data (FAB): 599 (MH⁺)

Example 73 ##STR123##

In the same manner as described in Example 66, 1.60 g of7-chloro-2-ethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 73a) and 1.18 g of7-chloro-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 73b) were obtained from 1.10 g of7-chloro-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 73a:

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.26 (3H, t), 2.58 (2H, q), 5.10 (2H, s)

(2) Mass spectrometric data (FAB): 647 (MH⁺)

Compound 73b

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.39 (3H, t), 2.86 (2H, q), 5.14 (2H, s)

(2) Mass spectrometric data (FAB): 647 (MH⁺)

Example 74 ##STR124##

In the same manner as described in Example 66, 0.91 g of7-bromo-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 1.00 g of7-bromo-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.40 (3H, t), 2.88 (2H, q), 5.17 (2H, s)

(2) Mass spectrometric data (FAB): 691 (MH⁺)

Example 75 ##STR125##

In the same manner as described in Example 66, 2.32 g of2-ethyl-7-methoxy-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 0.77 g of2-ethyl-7-methoxy-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.39 (3H, t), 2.86 (2H, q), 3.78 (3H, s), 4.94 (2H, s), 6.49 (1H, s)

(2) Mass spectrometric data (FAB): 643 (MH⁺)

Example 76 ##STR126##

In the same manner as described in Example 66, 0.12 g of ethyl[7-ethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetate(compound 76a) and 1.11 g of ethyl[7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetate(compound 76b) were obtained from 0.53 g of ethyl[7-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetate.

Compound 76a:

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.04 (3H, t), 1.24 (3H, t), 2.29 (2H, q), 3.66 (2H, s), 4.15 (2H, q),5.15 (2H, s)

(2) Mass spectrometric data (FAB): 699 (MH⁺)

Compound 76b

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.20 (3H, t), 1.27 (3H, t), 2.54 (2H, q), 3.88 (2H, s), 4.21 (3H, q),5.10 (2H, s)

(2) Mass spectrometric data (FAB): 699 (MH⁺)

Example 77 ##STR127##

In the same manner as described in Example 66, 1.02 g of6-ethoxy-2-ethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 77a) and 1.22 g of6-ethoxy-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 77b) were obtained from 1.80 g of6-ethoxy-2-ethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 77a:

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.29 (3H, t), 1.37 (3H, t), 2.62 (2H, q), 4.24 (2H, q), 4.89 (2H, s)

(2) Mass spectrometric data (FAB): 657 (MH⁺)

Compound 77 b

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.36 (3H, t), 1.44 (3H, t), 2.82 (2H, q), 4.17 (2H, q), 5.12 (2H, s),5.39 (1H, s)

(2) Mass spectrometric data (FAB): 657 (MH⁺)

Example 78 ##STR128##

In the same manner as described in Example 66, 170 mg of2,7-diethyl-6-methoxymethyl-1-[[2'-(N-triphenylmethyltetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole(compound 78a) and 2.5 g of2,7-diethyl-6-methoxymethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole(compound 78b) were obtained from 1.0 g of2,7-diethyl-6-methoxymethyl-1H-pyrazolo[1,5-b][1,2,4]triazole.

Compound 78a:

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.17 (3H, t), 1.21 (3H, t), 2.57 (2H, q), 2.71 (2H, q), 3.21 (3H, s),4.37 (2H, s), 5.49 (2H, s)

(2) Mass spectrometric data (FAB): 685 (MH⁺)

Compound 78b

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.19-1.24 (6H, m), 2.56-2.67 (4H, m), 3.21 (3H, s), 4.45 (2H, s), 5.39(2H, s)

(2) Mass spectrometric data (FAB): 685 (MH⁺)

Example 79 ##STR129##

In the same manner as described in Example 66, 1.8 g of2,7-diethyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde(compound 79a) and 2.8 g of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde(compound 79b) were obtained from 1.7 g of2,7-diethyl-1H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde.

Compound 79a:

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

0.96 (3H, t), 1.32 (3H, t), 2.62-2.67 (4H, m), 5.09 (2H, s), 10.03 (1H,s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Compound 79b

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.40-1.44 (6H, m), 2.93-3.00 (4H, m), 5.70 (2H, s), 9.97 (1H, s)

(2) Mass spectrometric data (FAB): 669 (MH⁺)

Example 80 ##STR130##

In the same manner as described in Example 66, 1.1 g of2,7-diethyl-6-(2,2-dimethoxyethyl)-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 650 mg of2,7-diethyl-6-(2,2-dimethoxyethyl)-1H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.34 (3H, t), 1.39 (3H, t), 2.62 (2H, q), 2.84 (2H, d), 2.89 (2H, q),3.32 (6H, s), 4.35 (1H, t), 5.41 (2H, s)

(2) Mass spectrometric data (FAB): 729 (MH⁺)

Example 81 ##STR131##

A 240 mg portion of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehydewas dissolved in 7 ml of an ethanol-tetrahydrofuran (1:6) mixed solventto which, with cooling on an ice bath, was subsequently added 15 mg ofsodium borohydride. With cooling on an ice bath, the mixture was stirredfor 30 minutes, mixed with 5 ml of water and then adjusted to an acidicrange with 1N of hydrochloric acid. After removing the solvent bydistillation under a reduced pressure, the resulting residue wasdissolved in ethyl acetate and washed with water and saturated sodiumchloride aqueous solution in that order, and the resulting organic layerwas dried over anhydrous magnesium sulfate.

Thereafter, the solvent was removed by distillation under a reducedpressure to obtain 240 mg of2,7-diethyl-6-hydroxymethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.22 (3H, t), 1.39 (3H, t), 2.54 (2H, br), 2.90 (2H, q), 4.55 (2H, s),5.49 (2H, s)

(2) Mass spectrometric data (FAB): 671 (MH⁺)

Example 82 ##STR132##

A mixture consisting of 1.11 g of7-ethyl-2-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole,63 ml of methanol and 7 ml of acetic acid was heated for 3 hours underreflux.

After removing the solvent by distillation under a reduced pressure, thethus obtained residue was mixed with toluene and again subjected todistillation under a reduced pressure. Thereafter, the resulting residuewas crystallized from ethyl acetate to give 0.64 g of7-ethyl-2-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolein the form of colorless crystals.

(1) Melting point: 169°-170.5° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈.0.1CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.71        5.93    26.60                                         found:     66.74        5.98    26.56                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.90 (3H, t), 1.21 (3H, t), 1.67 (2H, m), 2.58 (2H, t), 5.35 (2H, s),7.05 (2H, d), 7.19 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 83 ##STR133##

In the same manner as the procedure of Example 82, 0.49 g of2-butyl-7-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 0.80 g of2-butyl-7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 167°-169° C.

(2) Elemental analysis data (for C₂₄ H₂₆ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              67.58        6.14    26.27                                         found:     67.33        6.14    25.98                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.88 (3H, t), 1.21 (3H, t), 1.32 (2H, m), 1.64 (2H, m), 2.61 (2H, t),5.35 (2H, s), 7.06 (2H, d), 7.19 (2H, d)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 84 ##STR134##

In the same manner as the procedure of Example 82, 0.64 g of2-cyclopropyl-7-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.20 g of2-cyclopropyl-7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 139.5°-141° C.

(2) Elemental analysis data (for C₂₃ H₂₂ N₈.0.3H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.43        5.48    26.94                                         found:     66.59        5.48    26.70                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.80-0.90 (4H, m), 1.19 (3H, t), 1.94 (1H, m), 5.34 (2H, s), 7.07 (2H,d), 7.19 (2H, d)

(4) Mass spectrometric data (FAB): 411 (MH⁺)

Example 85 ##STR135##

In the same manner as the procedure of Example 82, 0.77 g of2,7-diethyl-6-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.30 g of2,7-diethyl-6-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 149°-152° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈.0.2CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              66.46        6.00    26.05                                         found:     66.53        5.99    26.06                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.18 (3H, t), 1.22 (3H, t), 2.30 (3H, s), 2.49 (2H, q), 2.63 (2H, q),5.41 (2H, s), 7.05 (2H, d), 7.08 (2H, d)

(4) Mass spectrometric data (FAB): 413 (MH⁺)

Example 86 ##STR136##

In the same manner as the procedure of Example 82, 0.71 g of2,6,7-triethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.20 g of2,6,7-triethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 207°-209° C. (decomposition)

(2) Elemental analysis data (for C₂₄ H₂₆ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              67.58        6.14    26.27                                         found:     67.85        6.21    26.13                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.06 (3H, t), 1.20 (3H, t), 1.22 (3H, t), 2.51 (2H, q), 2.63 (2H, q),2.72 (2H, q), 5.43 (2H, s), 7.05 (4H, s)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 87 ##STR137##

In the same manner as the procedure of Example 82, 0.50 g of2,7-diethyl-6-propyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 0.80 g of2,7-diethyl-6-propyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 212°-213° C. (decomposition)

(2) Elemental analysis data (for C₂₅ H₂₈ N₈)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              68.16        6.41    25.43                                         found:     68.20        6.50    25.21                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

0.89 (3H, t), 1.20 (3H, t), 1.22 (3H, t), 1.46 (2H, m), 2.60-2.70 (4H,m), 5.41 (2H, s), 7.04 (4H, t)

(4) Mass spectrometric data (FAB): 441 (MH⁺)

Example 88 ##STR138##

In the same manner as the procedure of Example 82, 0.41 g of2-methyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 0.70 g of2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 225°-228° C. (decomposition)

(2) Elemental analysis data (for C₁₉ H₁₆ N₈.0.2CH₃ COOCH₂ CH₃)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.59        4.74    29.96                                         found:     63.73        4.69    30.18                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

2.29 (3H, S), 5.47 (2H, s), 6.20 (1H, d), 7.07 (2H, d), 7.19 (2H, d),7.93 (1H, d)

(4) Mass spectrometric data (FAB): 357 (MH⁺)

Example 89 ##STR139##

In the same manner as the procedure of Example 82, 0.61 g of7-chloro-2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.05 g of7-chloro-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 181°-182.5° C. (decomposition)

(2) Elemental analysis data (for C₂₀ H₁₇ ClN₈)

    ______________________________________                                                 C (%) H (%)      N (%)   Cl (%)                                      ______________________________________                                        calculated:                                                                              59.33   4.23       27.68 8.76                                      found:     59.30   4.20       27.83 8.99                                      ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.23 (3H, t), 2.67 (2H, q), 5.46 (2H, s), 7.09 (2H, d), 7.24 (2H, d),8.22 (1H, s)

(4) Mass spectrometric data (FAB): 405 (MH⁺)

Example 90 ##STR140##

In the same manner as the procedure of Example 82, 0.40 g of7-bromo-2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained the form of colorless crystals from 0.70 g of7-bromo-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 186°-188° C. (decomposition)

(2) Elemental analysis data (for C₂₀ H₁₇ BrN₈)

    ______________________________________                                                 C (%) H (%)      N (%)   Br (%)                                      ______________________________________                                        calculated:                                                                              53.46   3.81       24.94 17.78                                     found:     53.19   3.82       24.82 17.88                                     ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.23 (3H, t), 2.67 (2H, q), 5.47 (2H, s), 7.10 (2H, d), 7.25 (2H, d),8.22 (1H, s)

(4) Mass spectrometric data (FAB): 449 (MH⁺)

Example 91 ##STR141##

In the same manner as the procedure of Example 82, 0.47 g of2-ethyl-7-methoxy-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless crystals from 1.81 g of2-ethyl-7-methoxy-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Elemental analysis data (for C₂₁ H₂₀ N₈ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              62.99        5.03    27.98                                         found:     62.91        5.01    27.87                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.22 (3H, t), 2.65 (2H, q), 3.81 (3H, s), 5.20 (2H, s), 7.05 (2H, d),7.21 (2H, d)

(3) Mass spectrometric data (FAB): 401 (MH⁺)

Example 92 ##STR142##

A mixture consisting of 1.02 g of ethyl[7-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetate,45 ml of methanol and 5 ml of acetic acid was heated for 2 hours underreflux. The solvent was removed by distillation under a reducedpressure, the thus obtained residue was mixed with toluene, and themixture again subjected to distillation under a reduced pressure.

Thereafter, the resulting residue was subjected to silica gel columnchromatography. Elution with a gradient from chloroform only tomethanol-chloroform (1:9, v/v) gave 0.62 g of ethyl[7-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetatein the form of colorless amorphous foamy material.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.17 (3H, t), 1.22 (3H, t), 2.53 (2H, q), 3.72 (2H, s), 4.08 (2H, q),5.39 (2H, s), 7.06 (2H, d), 7.20 (2H, d), 7.73 (1H, s)

(2) Mass spectrometric data (FAB): 457 (MH⁺)

Example 93 ##STR143##

A mixture consisting of 0.44 g of ethyl[7-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]acetate,27 ml of ethanol and 3 ml of 1N sodium hydroxide aqueous solution washeated for 2 hours under reflux. The reaction mixture was concentratedunder a reduced pressure and the resulting residue was dissolved in 10ml of water.

With cooling on an ice bath, the thus prepared solution was adjusted topH 2 with 0.5N hydrochloric acid aqueous solution, and the thusprecipitated solid material was collected by filtration to give 0.37 gof[7-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazol-2-yl]aceticacid in the form of colorless amorphous solid.

(1) Elemental analysis data (for C₂₂ H₂₀ N₈ O₂.0.7H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              59.91        4.89    25.41                                         found:     59.84        4.56    25.48                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.22 (3H, t), 2.54 (2H, q), 3.65 (2H, s), 5.40 (2H, s), 7.07 (2H, d),7.21 (2H, d), 7.75 1H, s)

(3) Mass spectrometric data (FAB): 429 (MH⁺)

Example 94 ##STR144##

In the same manner as the procedure of Example 92, 0.59 g of6-ethoxy-2-ethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained in the form of colorless amorphous foamy material from 1.08g of6-ethoxy-2-ethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20 (3H, t), 1.36 (3H, t), 2.60 (2H, q), 4.23 (2H, q) 5.17 (2H, s) 5.68(1H, s) 7.05 (2H, d), 7.13 (2H, d)

(2) Mass spectrometric data (EI): 414 (M⁺)

Example 95 ##STR145##

In the same manner as the procedure of Example 82, 480 mg of2,7-diethyl-6-methoxymethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 1.0 g of2,7-diethyl-6-methoxymethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 192°-194° C.

(2) Elemental analysis data (for C₂₄ H₂₆ N₈ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              65.14        5.92    25.32                                         found:     65.16        5.97    25.33                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.22 (6H, t), 2.60 (2H, q), 2.65 (2H, q), 3.24 (3H, s), 4.56 (2H, s),5.44 (2H, s), 7.05 (2H, d), 7.14 (2H, d)

(4) Mass spectrometric data (FAB): 443 (MH⁺)

Example 96 ##STR146##

In the same manner as the procedure of Example 82, 300 mg of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehydewas obtained from 800 mg of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde.

(1) Melting point: 193°-195° C.

(2) Elemental analysis data (for C₂₃ H₂₂ N₈ O.0.2AcOEt)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.37        5.36    25.23                                         found:     64.54        5.40    25.42                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.26 (3H, t), 1.33 (3H, t), 2.74 (2H, q), 2.98 (2H, q), 5.72 (2H, s),7.04 (2H, d), 7.13 (2H, d), 10.09 (1H, s)

(4) Mass spectrometric data (FAB): 427 (MH⁺)

Example 97 ##STR147##

In the same manner as the procedure of Example 82, 420 mg of2,7-diethyl-6-(2,2-dimethoxyethyl)-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 1.1 g of2,7-diethyl-6-(2,2-dimethoxyethyl)-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 185°-187° C.

(2) Elemental analysis data (for C₂₆ H₃₀ N₈ O₂.0.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.94        6.23    22.94                                         found:     63.95        6.22    22.93                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.22 (6H, t), 2.53 (2H, q), 2.64 (2H, q), 3.00 (2H, d), 3.21 (6H, s),4.36 (1H, t), 5.45 (2H, s), 7.02 (2H, d), 7.06 (2H, d)

(4) Mass spectrometric data (FAB): 486 (MH⁺)

Example 98 ##STR148##

In the same manner as the procedure of Example 82, 100 mg of2,7-diethyl-6-hydroxyethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolewas obtained from 800 mg of2,7-diethyl-6-hydroxymethyl-5-[[2'-(N-triphenylmethyl-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.

(1) Melting point: 182°-184° C.

(2) Elemental analysis data (for C₂₃ H₂₄ N₈ O.0.1H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              64.20        5.67    26.04                                         found:     64.23        5.65    26.02                                         ______________________________________                                    

(3) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.21 (3H, t), 1.22 (3H, t), 2.58 (2H, q), 2.63 (2H, q), 4.57 (2H, s),5.46 (2H, s), 7.04 (2H, d), 7.16 (2H, d)

(4) Mass spectrometric data (FAB): 429 (MH⁺)

Example 99 ##STR149##

A 630 mg portion of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehydewas suspended in 20 ml of ethanol. Next, 240 mg of sodium hydroxide wasallowed to react with 500 mg of silver nitrate in 2 ml of water whichwas cooled on an ice bath, and the thus prepared solution was added tothe above reaction solution to carry out 1 hour of heating under reflux.After spontaneous cooling of the thus obtained reaction solution,insoluble materials were removed by filtration and the resultingfiltrate was evaporated to dryness under a reduced pressure.

The thus obtained residue was dissolved in 2 ml of water, and thesolution was adjusted to an acidic range with 1N hydrochloric acid andthen subjected to extraction with ethyl acetate. The organic layer wasdried over anhydrous magnesium sulfate, and the solvent was removed bydistillation under a reduced pressure to give 190 mg of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]'triazole-6-carbonicacid.

(1) Melting point: 171°-174° C.

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.24 (3H, t), 1.26 (3H, t), 2.71 (2H, q), 2.91 (2H, q), 5.73 (2H, s),7.04 (2H, d), 7.09 (2H, d)

(3) Mass spectrometric data (FAB): 443 (MH⁺)

Example 100 ##STR150##

(1) A 150 ml portion of methanol was added to a mixture consisting of8.39 g of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazoleand 1.46 g of potassium carbonate, and the mixture was heated untilsolid materials were dissolved. The solvent was removed by distillationunder a reduced pressure, and the resulting residue was crystallizedfrom ethyl acetate to give 8.96 g of crude crystals of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolepotassium salt.

(2) A 11.8 g portion of the crude crystal of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolepotassium salt was dissolved in 90 ml of ethyl acetate with heating,followed by filtration while hot. A 0.49 nil portion of water was addedto the resulting filtrate which was stirred vigorously. Thereafter, thethus precipitated crystals were collected by filtration to give 11.5 gof2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazolepotassium salt.

(1) Elemental analysis data (for C₂₂ H₂₁ N₈ K.H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              58.13        5.10    24.65                                         found:     58.29        5.13    24.81                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.20-1.24 (6H, m), 2.52 (2H, q), 2.65 (2H, q), 5.32 (2H, s), 7.07 (2H,d), 7.10 (2H, d), 7.65 (1H, s)

(3) Mass spectrometric data (FAB): 475 (M+K)⁺

Example 101 ##STR151##

A mixture consisting of 1.13 g of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde,30 ml of ethanol, 0.65 g of sodium cyanide, 5.30 g of manganese dioxideand 0.23 ml of acetic acid was stirred overnight at room temperature.The reaction mixture was filtered through celite and the resultingfiltrate was concentrated under a reduced pressure. The thus obtainedresidue was mixed with chloroform and again passed through celite. Theresulting filtrate was concentrated under a reduced pressure, andsubjected to silica gel column chromatography. Elution was conductedwith an ethanol-chloroform (2:23, v/v) mixed solvent. Fractionscontaining the compound of interest were concentrated under a reducedpressure, and the thus obtained residue was dissolved in an appropriatevolume of a mixed solution consisting of diluted sodium bicarbonateaqueous solution and ethanol, thereby adjusting the resulting solutionto weak alkaline side. After removing the solvent by distillation undera reduced pressure, the resulting residue was dissolved in 40 ml ofwater, and the solution was adjusted to pH 2 with 1N hydrochloric acid.Thereafter, the solid material thus precipitated was collected byfiltration to give 0.56 g of ethyl2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylate in the form of amorphous solid.

(1) Elemental analysis data (for C₂₅ H₂₆ N₈ O₂)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              63.82        5.57    23.81                                         found:     63.63        6.64    23.80                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.24-1.30 (9H, m), 2.73 (2H, q), 2.90 (2H, q), 4.36 (2H, q), 5.68 (2H,s), 7.05 (2H, d), 7.10 (1H, d)

(3) Mass spectrometric data (FAB): 471 (MH⁺)

Example 102 ##STR152##

A mixture consisting of 1.13 g of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde,20 ml of methanol, 0.65 g of sodium cyanide, 5.30 g of manganese dioxideand 0.23 ml of acetic acid was stirred for 3 days at room temperature.The reaction mixture was filtered through celite and the resultingfiltrate was concentrated under a reduced pressure. The thus obtainedresidue was mixed with chloroform and again passed through celite. Theresulting filtrate was concentrated under a reduced pressure, andsubjected to silica gel column chromatography. Elution was conductedwith a methanol-chloroform (3:17, v/v) mixed solvent. Fractionscontaining the compound of interest were concentrated under a reducedpressure, and the thus obtained residue was dissolved in 4 ml of ethylacetate. Thereafter, the thus prepared solution was stirred overnightwhile cooling on an ice bath, and the solid material thus precipitatedwas collected by filtration to give 0.48 g of methyl2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylatesodium salt in the form of amorphous solid.

(1) Elemental analysis data (for C₂₄ H₂₃ N₈ O₂ Na.0.7H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              58.70        5.01    22.82                                         found:     58.83        5.09    22.79                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (DMSO-d₆, TMS) δ (ppm):

1.24-1.27 (6H, m), 2.74 (2H, q), 2.89 (2H, q), 3.91 (3H, s), 5.67 (2H,s), 7.04 (2H, d), 7.06 (2H, d)

(3) Mass spectrometric data (FAB): 501 (M+Na)⁺

Example 103 ##STR153##

A mixture consisting of 8.83 g of2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylicacid, 60 ml of N,N-dimethylformamide, 2.82 ml of triethylamine and 5.66g of triphenylmethyl chloride was stirred overnight at room temperature.After removing the solvent by distillation under a reduced pressure, thethus obtained residue was mixed with 250 ml of ethyl acetate and thenwashed with 150 ml of water. Thereafter, the ethyl acetate layer wasstirred overnight at room temperature, and the solid material thusprecipitated was collected by filtration to give 6.98 g of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylicacid.

(1) Nuclear magnetic resonance spectrum DMSO-d₆, TMS) δ (ppm):

1.21-1.25 (6H, m), 2.70 (2H, q), 2.91 (2H, q), 5.68 (2H, s), 6.85 (6H,d), 7.01 (2H, d), 7.04 (2H, d)

(2) Mass spectrometric data (FAB): 683 (M--H)⁻

Example 104 ##STR154##

A mixture consisting of 4.50 g of ethyl 1-chloroethylcarbonate, 13.2 gof sodium iodide and 100 ml of acetonitrile was stirred for 45 minutesat an external temperature of 60° to 70° C. The solvent was removed bydistillation under a reduced pressure, and the thus obtained residue wasmixed with ether, followed by the removal of the formed salt byfiltration. The resulting filtrate was concentrated under a reducedpressure and mixed with 40 ml of acetone to prepare an acetone solutionof ethyl 1-iodoethylcarbonate.

On the other hand, 6.73 g of2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylicacid was dissolved in 0.1N ethanolic potassium hydroxide solution. Thesolvent was removed by distillation under a reduced pressure and theresulting residue was dissolved in 250 ml of acetone to which, withcooling on an ice bath, was subsequently added the previously preparedethyl 1-iodoethylcarbonate in a dropwise manner spending 10 minutes. Theresulting reaction mixture was stirred for 2 days at room temperatureand, after removing the solvent by distillation under a reducedpressure, subjected to silica gel column chromatography. Elution wasconducted with an ethyl acetate-n-hexane (3:7, v/v) mixed solvent togive 5.75 g of 1-ethoxycarbonyloxyethyl2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylate.

(1) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.28 (6H, t), 1.39 (3H, t), 1.63 (3H, d), 2.90 (2H, q), 2.97 (2H, q),4.20-4.24 (2H, m), 5.64 (1H, d), 5.68 (1H, d), 6.91 (6H, d), 6.92-7.07(5H, m)

(2) Mass spectrometric data (FAB): 801 (MH⁺)

Example 105 ##STR155##

A mixture consisting of 5.64 g of 1-ethoxycarbonyloxyethyl2,7-diethyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylate,230 ml of methanol and 12 ml of acetic acid was heated under reflux for3 hours. After removing the solvent by distillation under a reducedpressure, the resulting residue was subjected to silica gel columnchromatography. Elution was conducted with a methanol-chloroform (1:19,v/v) mixed solvent to give 3.76 g of 1-ethoxycarbonyloxyethyl2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylatein the form of amorphous foamy material.

(1) Elemental analysis data (for C₂₈ H₃₀ N₈ O₅.0.3H₂ O)

    ______________________________________                                                 C (%)      H (%)   N (%)                                             ______________________________________                                        calculated:                                                                              59.63        5.47    19.87                                         found:     59.64        5.43    19.85                                         ______________________________________                                    

(2) Nuclear magnetic resonance spectrum (CDCl₃, TMS) δ (ppm):

1.09 (3H, t), 1.24-1.28 (6H, m), 1.63 (3H, d), 2.64-2.72 (4H, m),4.14-4.20 (2H, m), 5.72 (1H, d), 5.77 (1H, d), 6.90-7.00 (5H, m)

(3) Mass spectrometric data (FAB): 559 (MH⁺)

Compounds shown in Table 3 can be produced in the same manner asdescribed in Examples 104 and 105 using corresponding alkylating agents.

                  TABLE 3                                                         ______________________________________                                         ##STR156##                                                                   R.sup.5             R.sup.16                                                  ______________________________________                                         ##STR157##         C(Ph).sub.3                                                ##STR158##         H                                                          ##STR159##         C(Ph).sub.3                                                ##STR160##         H                                                          ##STR161##         C(Ph).sub.3                                                ##STR162##         H                                                          ##STR163##         C(Ph).sub.3                                                ##STR164##         H                                                          ##STR165##         C(Ph).sub.3                                                ##STR166##         H                                                         ______________________________________                                    

We claim:
 1. A pyrazolotriazole derivative represented by the generalformula: ##STR167## wherein each symbol means as follows; R¹, R³ and R₄: one of them represents a hydrogen atom, a biphenylmethyl group havinga tetrazolyl group which may be substituted by aralkyl, or a lower alkylgroup, and each of the remaining two has no substituent,R₂ : a hydrogenatom, a biphenylmethyl group having a tetrazolyl group which may besubstituted by aralkyl, a cycloalkyl group, or a lower alkyl group whichmay be substituted by hydroxyl, lower alkoxy, carboxyl or loweralkoxycarbonyl, and R⁵ and R₆ : these may be the same or different fromeach other, and each represents a hydrogen atom, a halogen atom, abiphenylmethyl group having a tetrazolyl group which may be substitutedby aralkyl, a formyl group, a carboxyl group, an esterified carboxylgroup, a cycloalkyl group, a lower alkoxy group, or a lower alkyl groupwhich may be substituted by hydroxyl, formyl, carboxyl, lower alkoxy orlower alkoxycarbonyl, provided that at least one of R¹ to R⁶ is abiphenylmethyl group having a tetrazolyl group which may be substitutedby aralkyl, and the broken lines mean that the pyrazolotriazole ringforms three double bonds; or a pharmaceutically acceptable salt thereof.2. A pyrazolotriazole derivative of claim 1 represented by the generalformula: ##STR168## wherein each symbol means as follows; R^(2a) : alower alkyl group or a cycloalkyl group,R^(5a) : a hydrogen atom, aformyl group, a carboxyl group, an esterified carboxyl group or a loweralkyl group which may be substituted by hydroxyl, lower alkoxy orcarboxyl, R^(6a) : a lower alkyl group, and R¹⁶ : a hydrogen atom or anaralkyl group; or a salt thereof.
 3. A pyrazolotriazole derivative ofclaim 1 which is2,7-Diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazoleor a potassium salt thereof.
 4. A pyrazolotriazole derivative of claim 1which is2,7-Diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylicacid or an ester thereof.
 5. A pyrazolotriazole derivative of claim 1which is2,7-Diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxyaldehyde.6. A pyrazolotriazole derivative of claim 1 which is2,7-Diethyl-6-hydroxymethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole.7. A pharmaceutical composition which comprises a pharmacologicallyeffective amount of the pyrazolotriazole derivative or apharmaceutically acceptable salt thereof of claim 1 and apharmaceutically acceptable carrier.
 8. A pharmaceutical compositioncontaining as the active ingredient a pyrazoiotriazole derivativerepresented by the general formula: ##STR169## wherein each symbol meansas follows; R¹, R³ and R⁴ : one of them represents a hydrogen atom, abiphenylmethyl group having a tetrazolyl group which may be substitutedby aralkyl, or a lower alkyl group, and each of the remaining two has nosubstituent,R² : a hydrogen atom, a biphenylmethyl group having atetrazolyl group which may be substituted by aralkyl, a cycloalkylgroup, or a lower alkyl group which may be substituted by hydroxylgroup, lower alkoxy, carboxyl or lower alkoxycarbonyl, and R⁵ and R⁶ :these may be the same or different from each other, and each representsa hydrogen atom, a halogen atom, a biphenylmethyl group having atetrazolyl group which may be substituted by aralkyl, a formyl group, acarboxyl group, an esterified carboxyl group, a cycloalkyl group, alower alkoxy group, a lower alkoxycarbonyl group, or a lower alkyl groupwhich may be substituted by hydroxyl, formyl, carboxyl, lower alkoxy orlower alkoxycarbonyl, provided that at least one of R¹ to R⁶ is abiphenylmethyl group having a tetrazolyl group which may be substitutedby aralkyl, and the broken lines mean that the pyrazolotriazole ringforms three double bonds, or a pharmaceutically acceptable salt thereof.9. A pharmaceutically composition according to claim 8 wherein theactive material is a therapeutic agent for treating hypertension orchronic heart failure.
 10. A pharmaceutical composition containingaccording to claim 8 which comprises as an active ingredient2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazoleor a potassium salt thereof.
 11. A pharmaceutical composition containingas the active active ingredient2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole-6-carboxylicacid or an ester thereof.
 12. A pharmaceutical composition of claim 7which comprises as an active component2,7-diethyl-5-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazoleor a potassium salt thereof.
 13. A method for imparting an AIIreceptor-blocking activity to a patient in need of such treatment whichcomprises administering to said patient an AII receptor-blockingeffective amount of the pharmaceutical composition of claim 7.